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New Findings in Alzheimer's Research

September 2001

By Angela Pirisi

Amyloid—cause or effect?

The next question following quickly in the tracks of such discoveries is whether getting rid of the plaques would also result in regaining some cognitive and memory functions and perhaps preventing further loss of one’s mental faculties. There are those who believe that plaques are the physical aftermath of Alzheimer’s that mark its destructive path, and that removing them may be like picking a scab off a wound without getting rid of the infection below. Others are convinced that the plaques literally lay down the foundation for Alzheimer’s disease to start up, in which case reversing them may be like removing bullets from a gun.

There is a great deal of research based on the latter speculation, which suggests that halting plaque formation and/or getting rid of existing plaques would aptly prevent or treat Alzheimer’s. A number of studies have given hope by suggesting that this is the case, as Canadian researchers at the University of Toronto’s Centre for Research in Neurodegenerative Diseases confirmed recently with their research, which involved testing cognitive ability in mice after administering an amyloid beta (Abeta) vaccine. Their results showed that dissolving about 50% of existing amyloid plaques does help to improve memory function, thereby lending support to findings by Schenk et al.9 The authors write that, “Evidence that Abeta immunization also reduces cognitive dysfunction in murine models of Alzheimer’s disease would support the hypothesis that abnormal Abeta processing is essential to the pathogenesis of Alzheimer’s disease, and would encourage the development of other strategies directed at the ‘amyloid cascade’.” Moreover, the reduction in cognitive dysfunction was observed with removing just 50% of the plaques.

Similarly, findings by researchers at the University of South Florida showed that vaccination with Abeta protected transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer’s disease.10 Compared to untreated transgenic mice (controls), the inoculated mice showed better cognitive performance in a series of maze tests, and performed equally well as non-transgenic (non-Alzheimer’s) mice.

Finding more clues

The questions may be complex, but researchers have been making remarkable headway in piecing together this insidious disease and devising ways to combat it. In fact, while Alzheimer’s research embarked on a humble journey two decades ago, the discoveries have come fast and furious since then. Dedicated scientists are learning increasingly more about the underpinnings of this disease by the day.

As far as determining risk factors, lots has been done in terms of weighing out the role of genetics. So far, scientists have identified several Alzheimer-associated genes, including amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). The latest findings with regards to APOE-4 (a mutated form of apolipoprotein E gene closely tied to Alzheimer’s) are from a UCLA study, which showed that those carrying the Alzheimer’s gene APOE-4 (ApolipoproteinE-4) had significantly lower function in specific areas of the brain located above and behind the temples, amounting to a 5% decline in brain functions at a two-year follow-up.

With regards to drug targets, many researchers are focusing on developing therapeutic approaches that inhibit certain key proteases within cells, beta- and gamma-secretase, which are believed to be pivotal in the formation of beta-amyloid. Last year, at the Society for Neuroscience’s annual meeting in New Orleans, scientists from Johns Hopkins University reported findings that showed beta-secretase to be responsible for forming the molecules that make up plaque within the brain’s nerve cells. Using knockout mice missing genes for beta-secretase, these investigators demonstrated that nerve cells lacking the enzyme did not form the plaque protein (beta amyloid).

Meanwhile, researchers at the University of Toronto reported last year on finding a protein, which may serve as a potentially new drug target. They showed that a protein molecule named nicastrin seems to play a key role in regulating how APP becomes fragmented and leads to the deposition of plaques. Earlier work by the same scientists had uncovered presnilin-1 and presnilin-2, implicating the proteins in causing two of the most insidious forms of Alzheimer’s.

  • Urakami K et al. Nippon Ronen Igakkai Zasshi 2001 Mar;38(2):117-20.
  • Small GW, et al. Proc Natl Acad Sci 2000 May 23;97(11):5696-5698.
  • Jhee S et al. Expert Opin Investig Drugs 201 Apr;10(4):593-605.
  • St. George-Hyslop P, et al. Nature 2000 Sep 7;407(6800):48-54.

The research


Whether plaque prevention or removal yields any mental benefits is only part of the question being explored today. Some researchers are still stuck on answering what is the definitive cause of Alzheimer’s disease. Since the 1980s, when it was discovered that tangles were made up of a protein called tau, and that plaques contained beta-amyloid, scientists have endlessly debated whether it’s tau or beta-amyloid (also referred to as BAP) that’s responsible for bringing on Alzheimer’s. Explains Snyder, “One camp promotes the Abeta peptide and the processing of the amyloid precursor protein as the key player in the development and progression of AD, while the other has its sights set on the tau protein, its biochemistry and tau neuronal cell biology related to tau. The NIA has always supported and continues to support fundamental research in both of these areas. The recent (1998) discovery of the tauopathies, a class of neurodegenerative and dementia diseases caused by mutations in the tau protein, has fueled the debate still more.”

In support of the BAP argument, researchers at Rockefeller University recently attempted to settle the controversy surrounding how much plaque build-up correlates with dementia and whether Abeta changes precede or follow changes in tau. They managed to show that amyloid beta-peptide Abeta-containing plaques were elevated in cases of early dementia and strongly related to cognitive decline too.11 In fact, state the authors, in the frontal cortex, Abeta was elevated even prior to the occurrence of significant tau pathology. They conclude by saying that Abeta plays an important role “in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation or cytotoxic effects of Abeta should be pursued.”

Amyloid plaque is just one focal point in Alzheimer’s research, however, as scientists also consider the importance of many other factors that may be involved in the development or progression of the disease, such as the tau protein and neurofibrillary tangles in the brain. Also being weighed are genetics, hormones, inflammation and oxidative stress. Each new discovery, no matter how seemingly small in the context of ultimately finding a cure, furnishes scientists with a better picture of how the disease develops while aiding them in defining genetic and biologic changes that underlie AD, identifying high-risk individuals, finding possible drug targets, and homing in on what characterizes normal aging patterns in the brain and age-related cognitive decline. At the very least, the new research by Bacskai et al. gives hope to proponents of the amyloid theory that they are on the right track. The greater hope is that reducing plaque formation and/or reversing plaque deposits will one day help to design therapies aimed at preventing or delaying the symptoms of Alzheimer’s. Next, the researchers at Massachusetts General Hospital would like to establish the level and quality of brain function in areas that have been cleared of plaques, in hopes of understanding how to improve brain function.


  1. Cole G, et al. J Neuroscience 2000 Aug 1;20(15):5709-5714.
  2. Kawas C, et al. Neurology 1997 June 48(6):1517-1521.
  3. Larkin M. Lancet 2001 May 12;357(9267):1505.
  4. Mega MS. Int J Neuropsychopharmacol 2000 Jul;3(7):3-12.
  5. Bacskai BJ, et al. Nat Med 2001 Mar;7(3):369-372.
  6. Wyss-Coray T, et al. Nat Med 2001 May;7(5):612-618.
  7. Schenk D, et al. Nature 1999 Jul 8;400(6740):173-177.
  8. Weiner HL, et al. Ann Neurol 2000 Oct;48(4):567-57.
  9. Janus C et al. Nature 2000 Dec 21-28;408(6815):979-982.
  10. Morgan D et al. Nature 2000 Dec 2000 Dec 21-28;408(6815):982-985.
  11. Naslund J et al. JAMA 2000 Mar 22-29;283(12):1571-1577.