Format

Send to

Choose Destination
Ageing Res Rev. 2014 Jan;13:10-2. doi: 10.1016/j.arr.2013.10.001. Epub 2013 Nov 16.

On the origin of Alzheimer's disease. Trials and tribulations of the amyloid hypothesis.

Author information

1
Department of Anatomy, Loma Linda University School of Medicine, Evans Hall B08, 24785 Stewart Street, Loma Linda, CA 92354, United States. Electronic address: mcastello@llu.edu.
2
Department of Anatomy, Loma Linda University School of Medicine, Evans Hall B08, 24785 Stewart Street, Loma Linda, CA 92354, United States. Electronic address: ssoriano@llu.edu.

Abstract

The amyloid cascade hypothesis, which implicates the amyloid Aβ peptide as the pathological initiator of both familial and sporadic, late onset Alzheimer's disease (AD), continues to guide the majority of research. We believe that current evidence does not support the amyloid cascade hypothesis for late onset AD. Instead, we propose that Aβ is a key regulator of brain homeostasis. During AD, while Aβ accumulation may occur in the long term in parallel with disease progression, it does not contribute to primary pathogenesis. This view predicts that amyloid-centric therapies will continue to fail, and that progress in developing successful alternative therapies for AD will be slow until closer attention is paid to understanding the physiological function of Aβ and its precursor protein.

KEYWORDS:

Alzheimer's disease; Amyloid beta; Neurodegeneration

PMID:
24252390
DOI:
10.1016/j.arr.2013.10.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center