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Cited by 161Alzheimer's disease research and treatmentsAutophagy in Disease and TherapyDementia and Cognitive Impairment Research

Activation of mTOR: a culprit of Alzheimer’s disease?

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Cai, Zhiyou, Zhou, Yingjun, Xiao, Ming, Yan, Liang-Jun, He, Wenbo·2015·Neuropsychiatric Disease and Treatment
DOI 10.2147/ndt.s75717PMC PMC4399516
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Abstract

Alzheimer's disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating amyloid precursor protein (APP) metabolism and upregulating β- and γ-secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt), glycogen synthase kinase 3 [GSK-3], AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau. Rapamycin, the inhibitor of mTOR, may mitigate cognitive impairment and inhibit the pathologies associated with amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD.

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  • EIF4E contributes to Tau hyperphosphorylation and Aβ accumulation.

    “EIF4E contributes to Tau hyperphosphorylation and Aβ accumulation. 50”

    From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [50]

    In “The downstream components of mTOR signaling associated with AD” (page unavailable), the review links phosphorylated eIF4E to hyperphosphorylated tau and suggests it contributes to neurofibrillary changes. It does not say eIF4E causes tau hyperphosphorylation or Aβ accumulation; the Aβ pathway discussed there involves eIF2α and BACE1 instead. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hyperactivation of mTOR signaling seen in TSC could contribute to increased tau protein aggregation and the development of 3R/4R positive tangles.

    “In particular, the hyperactivation of mTOR signaling seen in TSC could contribute to increased tau protein aggregation and the development of 3R/4R positive tangles.”

    From Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation (2022) · cites this paper as [3]

    The section “The activation of mTOR: an enhancer of the hyperphosphorylation of tau?” (page unavailable) says mTOR activation promotes tau pathology and neurofibrillary-tangle formation. It discusses this in the context of Alzheimer’s disease, not TSC, and does not identify the tangles as 3R/4R positive. The TSC-specific and 3R/4R parts of the claim are therefore unsupported by our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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200 of 217 shown

Authors
Cai, Z., Zhou, Y., Xiao, M., Yan, L.-J., & He, W.
Affiliations
  • Hubei University of Medicine (CN)
  • Nanjing Medical University (CN)
  • University of North Texas Health Science Center (US)
Corresponding author
Cai, Zhiyou
ORCID
Venue
Neuropsychiatric Disease and Treatment
Publisher
Informa UK Limited
Published
2015-04
Volume
11
Pages
1015
ISSN
  • 1176-6328 (ISSN-L)
  • 1178-2021
DOI
10.2147/ndt.s75717
PMC
PMC4399516
OpenAlex
W2002225792
Cited by
161
References
248
Citations by year
2026: 16 · 2025: 18 · 2024: 17 · 2023: 16 · 2022: 14 · 2021: 16 · 2020: 13 · 2019: 9 · 2018: 16 · 2017: 12 · 2016: 12 · 2015: 2
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
Renmin Hospital of Wuhan University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
mTOR, Alzheimer's disease, amyloid-beta, tau hyperphosphorylation, autophagy, APP processing, beta-secretase, gamma-secretase, PI3K/Akt signaling, glycogen synthase kinase-3, AMPK, insulin-like growth factor I, rapamycin, neurofibrillary tangles, amyloid plaques, therapeutic target

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