Swerdlow · Journal of Alzheimer's disease : JAD 2010 · narrative review · n=?

The Alzheimer's disease mitochondrial cascade hypothesis.

Cited 566 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and mechanistic theory paper with no new human data

PubMed 20442494 · doi:10.3233/JAD-2010-100339 · record verified 2026-08-27

What was done

This is a narrative review and theoretical perspective paper outlining the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD). The authors synthesize literature examining how inherited baseline mitochondrial durability interacts with aging to trigger hallmark AD pathologies, such as tau phosphorylation and amyloid-beta amyloidosis.

What was found

The abstract reports no numerical or quantitative data. It narratively highlights lines of evidence supporting the hypothesis, such as endophenotype studies suggesting a maternal genetic component and the limited clinical efficacy observed with amyloid-reducing therapies.

Why it matters

It offers an alternative conceptual framework prioritizing mitochondrial dysfunction as the primary driver of late-onset sporadic AD, directing focus toward novel upstream therapeutic targets.

Limits

The abstract describes a narrative theory and review paper presenting no new primary empirical data, quantitative meta-analyses, or systematic review methodology.

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