Read This First!

Hello, AlzClub and AlzheimerCode are not-for-profit web sites for non-censored ideas, news, research, technology and clinics on Alzheimer's disease and related disorders. Both are run personally by me, Alexei Koudinov, MD, PhD, DrSci, well known for his Alzheimer's and basic science research, and for battling against the corruption of Alzheimer's field, to protect public interest. Few examples are under must read links above, most notable of which are correspondence with the Wall Street Journal that yielded three WSJ articles on Alzheimers, Security and Exchange Commission (SEC) and Written Evidence to UK Parliamentary committee. My contrubution to Alzheimer's research is summarized in cholesterol failure hypothesis of Alzheimer's and in the series of publications here. - With love, Alexei Koudinov

Alzforum Professional News & Views

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December 28, 2010

To Gemma. In memory of Mark

Produced on December 28, 2010, Mark's Day 9.

Side bar Eulogy for Mark Smith by George Perry, Wenquan Zou, and an excerpt of memories by Nate Berger is accompanied by Alex Koudinov love song on melody of not recorded song "Grown old with you" by John Lennon. Russian lyrics was written in 4+10 minutes on 8 and 11 October 2010. The song was originally dedicated to Alex Koudinov children, brothers, sister, a woman, and John Lennon 70th Birthday, and written for a sister (all, thanks God, are doing well), and is now re-dedicated to Gemma in memory of Mark. Translation of lyrics into English is provided at the end of this video clip. Sound Recording virtually made via software programming at Abbey Road Studio 1, London. To experience the sound of a listener in a studio, please download surround edition of the song. Surround sound 5.1 is available for download as Dolby Digital 5.1, 6 channel .wav or 6 channel .wma files, the link for a free VLC player is provided

Please visit Journal of Alzheimer's disease memorial web page In Memory: Mark A. Smith at to read Mark's guestbook memories by friends and colleagues.

December 24, 2010

In memory: Mark Smith, 1965 - 2010

by Alexei Koudinov, MD, PhD, DrSci

3D tagged/enabled video at youtube

How to view 3D video?

To view the video above please use 3D glasses. Otherwise, push 3D buttom (to appear after the playback start) at right of youtube player navigation bar to explore other viewing options.

I recommend, however, using 3D video below, programmed for viewing with no 3D red/green glasses (this video has no 3D tag and is intended to be viewed with no 3D glasses). I find this is not tiring for eyes and of brighter colors. The player below is of smaller size then standard youtube player, as it is more appropriate to easy catch 3D image for my eyes.

Stereographic video below has two separate image fields arranged side-by-side. The user is required to force his or her eyes either to cross, or to diverge, so that the two images appear to be three. Then as each eye sees a different image, the effect of depth is achieved in the central image of the three. It may take certain time to "see" a 3D image. Please don't "focus" on either video images, look ahead (beyond the screen) at the center, it takes less then a second for me to see 3D video at the player below:

3D video with no Youtube 3D tag enabled

Sound Recording and 3D motion pictures of 23 December 2010 5PM Jerusalem time by Alexei Koudinov. Melody by Tomaso Albinone, Adagio in G Minor. Candle is from Golgoga of the Holy Sepulture Church, Jerusalem.

Quoting news of 21 December 2010:

"As shocked researchers notify each other privately, the Alzforum editors are saddened to inform the community at large that Mark Smith died last Sunday.

According to the Cleveland Plain Dealer, Smith, a prolific and outspoken researcher on Alzheimer’s disease and the biology of aging, was walking home at about 2 a.m. from an early Christmas party at a local tavern, when a man, who had apparently been at the tavern as well that night, struck him from behind and left the scene. Another motorist noticed the body of a man lying in the road, notified the police, and Smith was pronounced dead at a local hospital shortly thereafter. Incredibly, the driver was later found dead in his home or his car, according to various early news reports (see, e.g., The News-Herald). Police are investigating.

Mark Smith was well known to Alzforum readers. Starting in 2002, he became a frequent commentator and co-led ARF Live discussions as early as 1999.

Born in 1965, Smith grew up in England, trained there and in Vienna, Austria, and then began his U.S. career with a postdoctoral position in 1992 in the lab of George Perry at Case Western Reserve University in Cleveland, Ohio. Smith rose through the ranks at Case Western, where he was professor of pathology. In 2006, Perry moved on to become dean at the University of Texas at San Antonio, but the two continued to work together closely. “We exchanged 20 e-mails per day and spoke daily on the phone, the last time Friday,” said Perry.

Smith and Perry coauthored some 500 papers and shared the work of editor-in-chief of the Journal of Alzheimer’s Disease. They co-edited, with Jesus Avila and June Kinoshita, the centennial book Alzheimer’s Disease, A Century of Scientific and Clinical Research, IOS Press, 1996. “Mark and I were indistinguishable in many ways. We worked on everything together,” said Perry. Indeed, a follow-up to this book, chronicling the major discoveries in AD research in the years since 1996, is already in planning; Perry will dedicate it to Smith.

Smith’s main contributions to the understanding of Alzheimer’s disease lie in the areas of oxidative stress and the cell cycle...

Also see: | be continued with personal address to Mark

December 21, 2010

Mark Smith, 45, Is Struck and Killed by Hit-and-Run Driver

Original article: World-renowned researcher fatally struck while walking, driver found dead. (20 December 2010) [FullText | Video]

Also see another 5ABC News video: WEWS News Staff. Alzheimer’s researcher, Case Western Reserve University professor mourned around world: Wife wants professor remembered as true scientist (21 December 2010) [Video]

BAINBRIDGE TOWNSHIP, OH (WOIO) - An investigation is underway after a deadly hit and run accident.

19 Action News has learned that Dr. Mark A. Smith, a well-respected and world renowned researcher, was walking Eastbound on Chagrin Road shortly after 2AM Sunday when he was struck by a vehicle.

The 45-year-old Bainbridge Township father of two was rushed to the Solon Medical Campus, where he was pronounced death.

Police found the car that fatally struck Dr. Smith a short time later on Ober Lane in Bainbridge Township. The driver of the car, 50-year-old Daniel V. Neesham, was found death at his home.

The Bainbridge Police Department has no conclusion on cause of death for either person and the cause of the accident is still being investigated. Investigators are waiting on toxicology and autopsy reports before they can determine a cause of death for the men.

November 10, 2010

Why there is no cure for Alzheimer's disease?

Based on Society for Neuroscience Ethics in Neurosciences Abstract 2010:

Koudinov, Alexei. Why ethical and policy issues topic of the Society for Neuroscience annual meetings is overdue? Program No. 28.4. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Available online at

Neuroscience is a human activity that has lots of features only insiders can talk about with confidence. While general public may consider science is a privilege of those with high IQ, for many behind a university campus wall (or commercial lab secrecy) it is a matter of surviving, battling for funds, lab space, equipment access, and tenure. It is so great to have a confidence you are set up until a pension age. It was long time ago that you had a scientific quest excitement and late night lab hours of experimentation. Surely, you built your research on the data by others, heavily quoted a field leader, prominent Professor of the national premier research center you dreamed about as a postdoc or a faculty member. You could not know that this Professor had industry appointments and that he sold his million dollar stock shortly before the clinical trial on devastating human brain disorder failed (1). Well, you thought this failure could be a failure of the major theory of the disease. But who cares? A number of years ago you read an article in the Wall Street Journal (2) that called this theory a dogma retarding the development of the true disease cure. Would it be practical to you to combat the field corruption? Can one be a warrior? The natural answer for you as an ordinary human being is not: NOT at a postdoc time, because otherwise who of the field leadership would say “yes” to your tenure promotion and approval? NOT now (when you are a senior professor) because you have so many ties. Our World is in fact small, so, you take your tenure/grants as a fragile substance and prefer to be not so loud. You recall five years ago or so British Parliament published written evidence, a fact based encyclopedia of the corruption in your research field (3). But its’ impact is remote, as no one wants to take ethical issues seriously or talk on them openly. Several no-response open statements by a caring scientist to US Office of Research Integrity ORI, SEC and British Office of Fair Trading are all examples that in neurosciences patients are forgotten, commercial interests or one’s Ego are ruling (1). Well, you hope the SFN takes a leadership by introducing new annual meeting topic of Ethical issues in Neurosciences, and that as of now evidence based facts of wrongdoing will be not that easy to hide. Openness means change for good. Good in science means public non-private interest in scientific findings.



September 06, 2010

Eli Lilly drug Semagacestat failure means amyloid theory of Alzheimer's disease is a bankrupt

Dr. Bill E. Beckwith. Memory Minute: Drug failure casts doubt on Alzheimer’s theory. (25 Aug 2010)

Excerpt: Do we really have a breakthrough in diagnosis and treatment of Alzheimer’s disease? In our desperation for a cure, we have gotten ahead of biology and cast all of our hopes on the amyloid hypothesis ignoring the complexity of Alzheimer’s disease.

The amyloid hypothesis drives a multitude of clinical trials currently underway by pharmaceutical companies to find the cure for Alzheimer’s disease. Simply stated, the hypothesis proposes that build up of beta amyloid, an abnormal protein in the brain, is the cause of Alzheimer’s disease. Hence, treatments are sought that either stop or reverse the production of amyloid proteins in the brain. One of the medications under investigation was semagacestat, a drug developed by Lilly Pharmaceuticals.

The trials had advanced to the point where there were 2,600 patients enrolled in the clinical trials comparing semagacestat with a placebo. This medication attacks the abnormal amyloid. In theory, this is a good thing. However, the trials were terminated because the results indicated (1) that the medication did not slow the disease as expected, (2) the medication made cognition worse, and (3) the medication made treated patients less able to care for their personal needs. This led to many commentaries defending the amyloid hypothesis despite this important failure. This is a natural reaction to information that goes contrary to one’s beliefs. We regroup and find new ways to support our belief and minimize or ignore contrary evidence.

But in this case, the failure of semagacestat should cast doubt on the amyloid theory. We need to pursue the science behind this theory and its failure but we need to be careful in moving ahead with a single minded theory. This could be a costly blind alley. As discussed ...earlier... the amyloid hypothesis has a number of other problems. For example, there are other data from clinical trials with amyloid drugs that reverse the buildup of beta amyloid but have no clinical benefit.

Furthermore, a substantial number of people develop enough plaques as they age that they meet the pathological criteria for Alzheimer’s disease on autopsy but have no symptoms of the disease... Read full article

September 02, 2010

Unabridged Alzheimer's University review article manuscript: amyloid beta improves memory through fixing cholesterol supply of brain cells

Alzheimer's amyloid beta improves memory in lab animal brain tissue: Amyloid beta, neural lipid metabolism, cholesterol and synaptic plasticity

This is Part 6 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3 | Part 4 | Part 5 | Part 6

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at:


Amyloid beta, neural lipid metabolism, cholesterol and synaptic plasticity

In line with our early reasoning that Abeta is an apolipoprotein constituent of lipoproteins (and as such may have a diverse function in lipid metabolism) we studies the effects of the synthetic analog of amyloid beta protein, peptide Abeta1-40 (thought to be a major form of soluble Abeta [[24]]) on lipid synthesis in the hippocampal slices of rodents using metabolic labeling with C14-acetate, a radioactive lipid precursor [[56]]. Over the prolonged incubation with the label slices remained viable and actively synthesized phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and cholesterol. Abeta treatment increased the synthesis of PC, PE and cholesterol on 33, 67 and 46 % above the control values (100 %), respectively.

Abeta1-40 also modulated the synthesis of choline-containing phospholipids (cPLs, namely phosphatidylcholine and sphingomyelin), the major neural membrane component, an integral part of the brain cholinergic system, and a reservoir for lipid second messengers. We traced the synthesis of cPLs with radioactive choline in the presence of Abeta1-40 and found that Abeta increases the synthesis of cPLs to 47% above the controls (no Abeta). These data imply that the modulation of neural lipids by Abeta can be mediated via different metabolic pathways [].

Additional experimentation showed that Abeta also enhanced the uptake of tritiated [3H]cholesterol by slices, ~32.5% in 6 hrs above the control value (100 %, no Abeta). We used two kinds of controls. First, we stimulated slices with 50 mM potassium (that models basic neural synaptic function), followed by a biochemical analysis of lipid synthesis with a radioactive label. K+ evoked depolarization did not significantly change specified above lipid syntheses (contrary to lipid peroxidation modification that we report below), suggesting that membrane depolarization, modeling basal synaptic activity and neurotransmission, do not enhance hippocampal lipid syntheses as it occurs during the treatment of slices with Abeta peptide, and after long-lasting synaptic enhancement (LTP), as verified by autoradiography of hippocampal slices after the metabolic labeling with radioactive lipid precursor [14C] acetate and the induction of the LTP with a tetanic stimulus (100 Hz, 1 sec) in stratum radiatum (SR) recording pathway of the CA1 [[56, 58]].

Therefore, we set to test the role for Abeta in the synaptic plasticity in brain slices from adult male rat hippocampus under the condition that we characterized previously with regard to cholesterol and phospholipid synthesis [[56, 59]]. The prolonged maintenance of slices in a test tube for about twenty hours in our experimental setup preserved synaptic function (input/output curve, I/O, a basic measure of synaptic function, Figure 1, inset) but abrogated synaptic plasticity (measured as LTP, Figure 1, Panel A). Synthetic homolog of the Abeta (1-40 amino acids’ molecule length, representing the major form of soluble Abeta[[24]], Panel B) rescued LTP while cholesterol synthesis inhibition with a statin abolished LTP restoration by the peptide [[59]].

LTP models synaptic plasticity that underlies learning and memory, and depends on cholesterol and phospholipids supply via synthesis and lipoprotein transport as well as membrane lipid peroxidation (discussed at length of this article). The above effect of Abeta may represent its biological function of activity-dependent sensing membrane physical and chemical properties that is translated into membrane lipid homeostasis modulation to fine tune current synaptic action. Our observation implies an intriguing perspective that Abeta protein is a functional player in an activity-dependent cholesterol neurochemical pathways and contributes to the knowledge base on the important role for Abeta in synaptic structure-functional plasticity shown by others [[21, 43, 44, 45, 46, 60, 61, 62]].

Our findings also support early formulation of our hypothesis that the change in Abeta biochemistry in Alzheimer's disease and related disorders is a functional (but NOT pathologic) compensatory phenomenon aiming to counterbalance impaired cholesterol dynamics and associated neurotransmission and synaptic plasticity [[56, 59, 63, 64]]. Such cholesterol mediated failure of synaptic function and neural degeneration in our view represents the cause of the major sporadic form of Alzheimer's disease [[56, 59, 63, 64, also see Scheme 1 in the following lecture]].

Amyloid beta restores memory in the model of hippocampal slices of lab animals

Figure 1. Effect of Alzheimer's Abeta1-40 on synaptic plasticity in CA1 area of adult rat hippocampus. A, Field excitatory postsynaptic potentials (fEPSPs) recorded from a single site in stratum radiatum of CA1 under the condition of the prolonged incubation of slices without the peptide Abeta1-40 (Control) or in the presence of the peptide (Abeta) are presented as normalized slopes versus time to yield LTP charts. Abeta1-40 peptide reversed the impairment of the LTP, a characteristic of synaptic plasticity, in slices subjected to 21+ hrs of maintenance ex-vivo, and made it statistically not different (P>0.05, nonparametric Mann-Whitney signed rank test, one-tailed) from the slices maintained for 6-8 hrs only [[56]]. Inset (I/O maximum) illustrates the maximum values of the input-stimulus/output-response (I/O) curves (indicative of basic synaptic function) that show no statistical differences (n=6, P>0.05, one-tailed) between slices maintained for a prolonged time with Abeta or without the peptide. D, Representative fEPSPs at the bottom right show that statin mevinolin (a cholesterol synthesis inhibitor) abolished LTP restoration by Abeta (for details and experimental protocol please see the text and the scheme in [[59]]). The presented waveforms are recorded during the baseline stimulation (1), immediately after the tetanic stimulus (2), as well as three (3) and twenty (4) minutes thereafter. Panel B illustrates amino acid sequence differences between rat and used in the study human Abeta1-40. “Stars” on the schematic hippocampal slice (Panel C) illustrate stimulating and recording electrodes positioning. The figure is reproduced by permission from the Neurobiology of Lipids, 1, 8 (2003), [[59]].


24. AR. Koudinov, NV. Koudinova, A. Kumar, R. Beavis, J. Ghiso. (1996) Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins. Biochem. Biophys. Res. Commun. (1996) 223:592-597

43. FR. Kamenetz, T. Tomita, DR. Borchelt, SS. Sisodia, T. Iwatsubo, R. Malinow. Activity dependent secretion of beta-amyloid: roles of -amyloid in synaptic transmission. Soc. Neurosci. Abstr. (2000) 26: 491.

44. HA. Pearson, C. Peers. Physiological roles for amyloid beta peptides. J. Physiol. (2006) 15: 5–10.

45. JP. Steinbach, U. Muller, M. Leist, ZW. Li, P. Nicotera, A Aguzzi. Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ. (1998) 5:858–866.

46. S. Lesne, C. Ali, C. Gabriel, N Croci, ET. MacKenzie, CG. Glabe, M. Plotkine, C. Marchand-Verrecchia, D. Vivien, A. Buisson. NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J. Neurosci. (2005) 25:9367–9377.

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at: Also available as slide show at:

57. NV. Koudinova, AR. Koudinov. Amyloid beta protein attenuates the synthesis of phospholipids containing choline: another effector of neural membrane homeostasis? Soc. Neurosci. Abst. online. (2002) Program No.884.2. Available at:

58. AR. Koudinov, NV. Koudinova. Cholesterols' role in synapse formation. Science (2002) 295: 2213.

59. AR. Koudinov, NV. Koudinova. Amyloid beta protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiol. Lipids (2003) 1: 8 Available at:

60. J. Wu, R. Anwyl, MJ. Rowan. beta-amyloid-(1-40) increases long-term potentiation in rat hippocampus in vitro. Europ. J. Pharm. (1995) 284: R1-R3.

61. J. Wu, R. Anwyl, MJ. Rowan. beta-amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. NeuroReport (1995) 6: 2409-2413.

62. PE. Schulz. beta-peptides enhance the magnitude and probability of long term potentiation. Soc. Neurosci. Abstr. (1996) 22: 2111.

63. AR. Koudinov, NV. Koudinova. Brain cholesterol pathology is the cause of Alzheimer's disease. Clin Med Health Res (2001) clinmed/2001100005. Available at:

64. AR. Koudinov, NV. Koudinova. Cholesterol, synaptic function and Alzheimer's disease. Pharmacopsychiatry (2003) S36: 107-12.

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at , also available as a slide show at (to be reprinted at Alzheimer's Code):

Link to this publication: amyloid-beta-lipids-cholesterol-synapse

Part 1 | Part 2 | Part 3 | Part 4 | Part 5 | Part 6

August 31, 2010

Unabridged Alzheimer disease article 5: Abeta and APP implicated in the function of peripheral synapses and the neuromuscular junction NMJ pathology

Amyloid beta and its precursor molecule APP implicated in the function of peripheral synapses and the neuromuscular junction (NMJ) pathology

Abeta and APP implicated in the function of peripheral synapses and the neuromuscular junction (NMJ) pathology

This is Part 5 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3 | Part 4 | Part 5

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at:


Alzheimer's Amyloid beta and its' precursor molecule APP implicated in the function of peripheral synapses and the neuromuscular junctions (NMJ) pathology

Further investigation is warranted to elucidate the normal role for amyloid beta protein (Abeta) and its’ precursor at peripheral synapses, neuromuscular junctions (NMJ) and NMJ pathologies (ex. inclusion-body myositis, IBM). Two basic observations include the study published more then a decade ago [[48]]. This was the first demonstration of APP and Abeta concentration postsynaptically at human neuro-muscular junctions, that led authors to conclude that “APP may have a role in normal junction biology and possibly in some diseases affecting NMJs”. Another study later showed that APP homolog in Drosophila (APPL) promotes synapse differentiation at the neuromuscular junction [[49]], leading the authors to propose a model “by which APPL, in conjunction with activity-dependent mechanisms, regulates synaptic structure and number”.

Recent comprehensive study performed analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. This research “found that APP deletion led to reduced paired-pulse facilitation [PPF, a measure of synaptic transmission and synaptic vesicles recycling efficacy] and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca(2+) channels.” Authors therefore proposed that APP modulates synaptic transmission at the NMJ by ensuring proper Ca(2+) channel function [[50]].

Another study [[51]] reported on an essential role of APP family of proteins in the development of neuromuscular synapses. “Mice deficient in APP and its homolog APP-like protein 2 (APLP2) exhibited aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals was dramatically reduced. [In agreement with the previous study by Yang L et al.[[Ref. 50]] ], these structural abnormalities were accompanied by defective neurotransmitter release and a high incidence of synaptic failure [[51]]. This is also in accord with the reduction of the synaptic vesicle density, active zone size, and docked vesicle number per active zone in submandibular ganglion synapses of mice lacking APP and APPLP2 demonstrated in lab animals with double gene deletions [[52]].

Another recent report demonstrated that APP is essential in regulating the presynaptic expression and activity of the high-affinity choline transporter (CHT), a molecule that mediates the rate-limiting step of cholinergic synaptic transmission in both the NMJ and central cholinergic neurons. Loss of APP was the cause of the aberrant localization of CHT at the neuromuscular synapses and reduced CHT activity at cholinergic projections. [[53]]

Interestingly, abnormal accumulation of APP and Abeta epitopes (as well as excessively phosphorylated tau in the form of paired helical filaments, PHF, see below) in vacuolated muscle fibers (VMF) is a characteristic feature of not just AD, but also the neuromuscular pathology such as IBM [[54, 55]]. Also important is the observation that in IBM there is an abnormal accumulation of a number of lipoprotein receptors (such as LDLR, VLDLR, LRP) and cholesterol within IBM vacuolated muscle fibers [[54]]. However, LDLR and VLDLR are also expressed at normal NMJ, suggesting “physiologic roles for them in transsynaptic signaling pathways and increased internalization of lipoproteins” at NMJ. Similarly, based on our physiological research with rat hippocampal slices, we earlier proposed that there is an activity-dependent demand for lipoprotein cholesterol and phospholipids at the central synapses [[56]]. Most important, the study by Jaworska-Wilczynska [[54]] confirms that there is a peripheral application of the functional crosstalk between Abeta, lipoproteins and cholesterol, that our own explanation of Abeta involvement in AD is about (see below).


48. V. Askanas, WK. Engel, RB. Alvarez. Strong immunoreactivity of beta-amyloid precursor protein, including the beta-amyloid protein sequence, at human neuromuscular junctions. Neurosci. Lett. (1992) 143: 96-100.

49. L. Torroja, M. Packard, M. Gorczyca , K. White, V. Budnik. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J. Neurosci. (1999) 19: 7793-7803.

50. L. Yang, B. Wang, C. Long, G. Wu, H. Zheng. Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses. Neuroscience (2007) 149(4):768-78.

51. P. Wang, G. Yang, DR. Mosier, P. Chang, T. Zaidi, YD. Gong, NM. Zhao, B. Dominguez, KF. Lee, WB. Gan, H. Zheng. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J. Neurosci. (2005) 25(5):1219-25.

52. G. Yang, YD. Gong, K. Gong, WL. Jiang, E. Kwon, P. Wang, H. Zheng, XF. Zhang, WB. Gan, NM. Zhao. Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci. Lett. (2005) 384(1-2):66-71.

53. B. Wang, L. Yang, Z. Wang, H. Zheng. Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc. Natl. Acad. Sci. USA (2007) 104(35):14140-5.

54. M. Jaworska-Wilczynska, GM. Wilczynski, WK. Engel, DK. Strickland, KH. Weisgraber, V. Askanas. Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle. Neurology (2002) 58: 438-445.

55. AR. Koudinov, NV. Koudinova, U. Beisiegel. Cholesterol homeostasis failure at neuromuscular junctions and CNS synapses: a unifying cause of synaptic degeneration? Neurology online. (2002) Available at

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at , also available as a slide show at (to be reprinted at Alzheimer's Code):

Link to this publication: amyloid-beta-app-implicated-in-synapse

Part 1 | Part 2 | Part 3 | Part 4 | Part 5

Latest research articles on Alzheimer’s