Amyloid Cascade into Clarity

Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal.

Here I recap the scientific and personal background of the delineation of the amyloid cascade hypothesis for Alzheimer's disease that I wrote with Gerry Higgins and the events leading to the writing of that influential review.

An amyloid-like cascade hypothesis for C9orf72 ALS/FTD

Expansion of a GGGGCC repeat in C9orf72 causes amyotrophic lateral sclerosis, frontotemporal dementia, or a combination of both. Bidirectional repeat transcripts sequester RNA-binding proteins into nuclear RNA foci. The repeat is translated into dipeptide repeat (DPR) proteins that are crucial for repeat-induced toxicity. DPRs inhibit the proteasome and sequester other proteins. These changes a...

Alzheimer disease therapy: can the amyloid cascade be halted?

A critical analysis of the 'amyloid cascade hypothesis'.

The 'amyloid cascade hypothesis' (ACH) is the most influential model of the pathogenesis of Alzheimer's disease (AD). The hypothesis proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of extracellular senile plaques (SP), tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia. Ever since th...

Alzheimer's Disease and the Amyloid Cascade Hypothesis: A Critical Review

Since 1992, the amyloid cascade hypothesis has played the prominent role in explaining the etiology and pathogenesis of Alzheimer's disease (AD). It proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs), neuronal cell death, and ultimately dementia. While there is substan...