Evidence map›Paper›PMID 37718817›Full record

ReviewJournal of Alzheimer's disease : JAD2023

Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer's Disease (Type 3 Diabetes).

Suzanne M de la Monte

Open access · greenAbstract readReview
In one paragraph

Review in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
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  12. Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?International journal of molecular sciences · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Suzanne M de la MonteFrom the Departments of Pathology and Laboratory Medicine, Medicine, Neurology and Neurosurgery, Rhode Island Hospital, Lifespan Academic Institutions, and the Warren Alpert Medical School of Brown University, Providence, RI, USA.
Lifespan · US

Funding

FASD Inhibition of ASPH-Notch Mediates Adolescent Cerebral White Matter Pathology-Potential Utility of Non-invasive Extracellular Vesicle AssaysR01AA011431 · NIAAA · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI SUZANNE M. DE LA MONTE · 1996 to 2026
$5.4M
Ethanol, IRS-1 Signaling and Neuronal MigrationR37AA011431 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2009 to 2018
$3.7M
Pathogenesis of Early- Versus Late-Stage Alcohol-Mediated White Matter DegenerationR01AA028408 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2021 to 2025
$1.7M
ETHANOL, INSULIN/IGF SIGNALING AND NEURONAL MIGRATIONR56AA011431 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2008 to 2008
$312k
NIAAA NIH HHS R01 AA011431NIAAA NIH HHS R01 AA028408NIAAA NIH HHS R37 AA011431NIAAA NIH HHS R56 AA011431
6 · The paper itself

Abstract

Malignant brain aging corresponds to accelerated age-related declines in brain functions eventually derailing the self-sustaining forces that govern independent vitality. Malignant brain aging establishes the path toward dementing neurodegeneration, including Alzheimer's disease (AD). The full spectrum of AD includes progressive dysfunction of neurons, oligodendrocytes, astrocytes, microglia, and the microvascular systems, and is mechanistically driven by insulin and insulin-like growth factor (IGF) deficiencies and resistances with accompanying deficits in energy balance, increased cellular stress, inflammation, and impaired perfusion, mimicking the core features of diabetes mellitus. The underlying pathophysiological derangements result in mitochondrial dysfunction, abnormal protein aggregation, increased oxidative and endoplasmic reticulum stress, aberrant autophagy, and abnormal post-translational modification of proteins, all of which are signature features of both AD and dysregulated insulin/IGF-1-mechanistic target of rapamycin (mTOR) signaling. This article connects the dots from benign to malignant aging to neurodegeneration by reviewing the salient pathologies associated with initially adaptive and later dysfunctional mTOR signaling in the brain. Effective therapeutic and preventive measures must be two-pronged and designed to 1) address complex and shifting impairments in mTOR signaling through the re-purpose of effective anti-diabetes therapeutics that target the brain, and 2) minimize the impact of extrinsic mediators of benign to malignant aging transitions, e.g., inflammatory states, obesity, systemic insulin resistance diseases, and repeated bouts of general anesthesia, by minimizing exposures or implementing neuroprotective measures.

Indexed as

Alzheimer DiseaseDiabetes MellitusBrainHumansInsulinSirolimusTOR Serine-Threonine KinasesInsulinSirolimusTOR Serine-Threonine KinasesAgingAlzheimer’s diseasebrainmTORneurodegenerationneuroinflammationtype 3 diabetesvascular diseasewhite matter

Identifiers

PMID37718817
PMCPMC10896181
OpenAlexW4386634298

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.