Alzheimer's disease: The right drug, the right time

See allHide authors and affiliations

Science  14 Dec 2018:
Vol. 362, Issue 6420, pp. 1250-1251
DOI: 10.1126/science.aau0437

eLetters is an online forum for ongoing peer review. Submission of eLetters are open to all. eLetters are not edited, proofread, or indexed.  Please read our Terms of Service before submitting your own eLetter.

Compose eLetter

Plain text

  • Plain text
    No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g.
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Statement of Competing Interests

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

  • RE: Need for a revised Amyloid Cascade Hypothesis for the right drug, the right time
    • Baris Topcular, Professor of Neurology, Istanbul Bilim University Medical Faculty

    Dear Sirs,

    Alzheimer's disease (AD) is the most common cause of age-related dementia and the number of patients with AD is increasing worldwide. Amyloid cascade hypothesis(ACH) provides a fundamental perspective for pathogenesis of AD. It is also strongly criticized due to failure of the clinical trials that experimented anti-amyloid drugs. Golde et al. brilliantly pointed out the importance of choosing the right drug and the right time for curing AD(1).

    In ACH model amyloid precursor protein(APP) is cleaved either by β-secretase followed by γ-secretase(amyloidogenic pathway) or α-secretase followed by γ-secretase(non-amyloidogenic pathway). It is the amyloidogenic pathway that ACH mostly focuses on as many studies showed the neurotoxic effects of β-amyloid.

    However there is growing evidence showing non-amyloidogenic pathway products have essential roles in several significant physiological processes including neurite growth, learning & memory, neural progenitor cell proliferation and neural survival(2,3,4,5). Studies by Small et al. and Allinquant et al. demonstrate that APP promotes neurite outgrowth(6,7). APP also plays a role in synoptogenesis(8). Zheng et al. showed that APP KO mice display neurological defisits that can be explained by effects on synaptogenesis(9). Zou et al. found that APP is important in maintaining constitutive and adaptive plasticity of dendritic spines in adult brain(10). sAPPα also demonstrates neuroprotective p...

    Show More
    Competing Interests: None declared.

Stay Connected to Science