Rapamycin and Alzheimer disease: a double-edged sword?

Julian M. Carosi, Timothy Sargeant

Research output: Contribution to journalComment/debate

4 Citations (Scopus)

Abstract

Numerous studies have reported that inhibition of MTOR (mechanistic target of rapamycin kinase) clearly reduces Alzheimer disease neuropathological hallmarks in mouse models. This has resulted in calls for the use of the MTOR inhibitor rapamycin for the treatment of dementia in humans. Unfortunately, intervention with rapamycin in these mouse studies commenced before or early in the appearance of these pathological hallmarks. Later in Alzheimer disease, when dementia actually manifests, the brain’s lysosomal system is severely damaged and treatment with rapamycin is likely to exacerbate this damage. We reassess literature described by a recent perspective article calling for the use of MTOR inhibition in dementia and conclude that rapamycin could be useful, but only in people who are in the earliest stages of Alzheimer disease. We contend that our interpretation of preclinical data concerning use of rapamycin in Alzheimer disease models is necessary if we are to avoid another failed Alzheimer disease drug trial. Abbreviations: AD: Alzheimer disease; APP: amyloid beta precursor protein; MAPT: microtubule associated protein tau; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1.

LanguageEnglish
Pages1460-1462
Number of pages3
JournalAutophagy
Volume15
Issue number8
DOIs
Publication statusPublished - 22 May 2019

Keywords

  • Alzheimer disease
  • autophagy
  • dementia
  • lysosome
  • rapamycin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Carosi, Julian M. ; Sargeant, Timothy. / Rapamycin and Alzheimer disease: a double-edged sword?. In: Autophagy. 2019 ; Vol. 15, No. 8. pp. 1460-1462.
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Rapamycin and Alzheimer disease: a double-edged sword? / Carosi, Julian M.; Sargeant, Timothy.

In: Autophagy, Vol. 15, No. 8, 22.05.2019, p. 1460-1462.

Research output: Contribution to journalComment/debate

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