Differential activation of the mTOR/autophagy pathway predicts cognitive performance in APP/PS1 mice

Rasika S. Vartak, Alexis Rodin, Salvatore Oddo

Research output: Contribution to journalArticle

Abstract

The molecular bases underlying cognitive impairments in Alzheimer's disease remain elusive. In this study, we sought to determine the molecular correlates of memory deficits in APP/PS1 mice, a widely used animal model of Alzheimer's disease. To this end, we tested 18-month-old APP/PS1 mice in the Morris water maze and ranked them by their spatial memory performance. We found that some APP/PS1 mice performed poorly, whereas others performed as well as nontransgenic mice. We took advantage of this intragroup variability to identify the best predictor of cognitive deficits. In this APP/PS1 cohort, soluble and insoluble amyloid-β levels did not correlate significantly with cognitive performance. However, we found that cognitive performance within the APP/PS1 group had a strong inverse correlation with Aβ plaque load and mammalian target of rapamycin activation and positively correlated with autophagy activation. Our data suggest that mammalian target of rapamycin signaling may account cognitive performance in APP/PS1 mice.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalNeurobiology of Aging
Volume83
DOIs
StatePublished - Nov 2019
Externally publishedYes

Fingerprint

Autophagy
Sirolimus
Alzheimer Disease
Memory Disorders
Amyloid
Animal Models
Water

Keywords

  • AD
  • Alzheimer's disease
  • Plaques
  • Tangles
  • tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Differential activation of the mTOR/autophagy pathway predicts cognitive performance in APP/PS1 mice. / Vartak, Rasika S.; Rodin, Alexis; Oddo, Salvatore.

In: Neurobiology of Aging, Vol. 83, 11.2019, p. 105-113.

Research output: Contribution to journalArticle

@article{004572d13ba94bb5b98b9c691d655d24,
title = "Differential activation of the mTOR/autophagy pathway predicts cognitive performance in APP/PS1 mice",
abstract = "The molecular bases underlying cognitive impairments in Alzheimer's disease remain elusive. In this study, we sought to determine the molecular correlates of memory deficits in APP/PS1 mice, a widely used animal model of Alzheimer's disease. To this end, we tested 18-month-old APP/PS1 mice in the Morris water maze and ranked them by their spatial memory performance. We found that some APP/PS1 mice performed poorly, whereas others performed as well as nontransgenic mice. We took advantage of this intragroup variability to identify the best predictor of cognitive deficits. In this APP/PS1 cohort, soluble and insoluble amyloid-β levels did not correlate significantly with cognitive performance. However, we found that cognitive performance within the APP/PS1 group had a strong inverse correlation with Aβ plaque load and mammalian target of rapamycin activation and positively correlated with autophagy activation. Our data suggest that mammalian target of rapamycin signaling may account cognitive performance in APP/PS1 mice.",
keywords = "AD, Alzheimer's disease, Aβ, Plaques, Tangles, tau",
author = "Vartak, {Rasika S.} and Alexis Rodin and Salvatore Oddo",
year = "2019",
month = "11",
doi = "10.1016/j.neurobiolaging.2019.08.018",
language = "English (US)",
volume = "83",
pages = "105--113",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Differential activation of the mTOR/autophagy pathway predicts cognitive performance in APP/PS1 mice

AU - Vartak, Rasika S.

AU - Rodin, Alexis

AU - Oddo, Salvatore

PY - 2019/11

Y1 - 2019/11

N2 - The molecular bases underlying cognitive impairments in Alzheimer's disease remain elusive. In this study, we sought to determine the molecular correlates of memory deficits in APP/PS1 mice, a widely used animal model of Alzheimer's disease. To this end, we tested 18-month-old APP/PS1 mice in the Morris water maze and ranked them by their spatial memory performance. We found that some APP/PS1 mice performed poorly, whereas others performed as well as nontransgenic mice. We took advantage of this intragroup variability to identify the best predictor of cognitive deficits. In this APP/PS1 cohort, soluble and insoluble amyloid-β levels did not correlate significantly with cognitive performance. However, we found that cognitive performance within the APP/PS1 group had a strong inverse correlation with Aβ plaque load and mammalian target of rapamycin activation and positively correlated with autophagy activation. Our data suggest that mammalian target of rapamycin signaling may account cognitive performance in APP/PS1 mice.

AB - The molecular bases underlying cognitive impairments in Alzheimer's disease remain elusive. In this study, we sought to determine the molecular correlates of memory deficits in APP/PS1 mice, a widely used animal model of Alzheimer's disease. To this end, we tested 18-month-old APP/PS1 mice in the Morris water maze and ranked them by their spatial memory performance. We found that some APP/PS1 mice performed poorly, whereas others performed as well as nontransgenic mice. We took advantage of this intragroup variability to identify the best predictor of cognitive deficits. In this APP/PS1 cohort, soluble and insoluble amyloid-β levels did not correlate significantly with cognitive performance. However, we found that cognitive performance within the APP/PS1 group had a strong inverse correlation with Aβ plaque load and mammalian target of rapamycin activation and positively correlated with autophagy activation. Our data suggest that mammalian target of rapamycin signaling may account cognitive performance in APP/PS1 mice.

KW - AD

KW - Alzheimer's disease

KW - Aβ

KW - Plaques

KW - Tangles

KW - tau

UR - http://www.scopus.com/inward/record.url?scp=85072756129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072756129&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2019.08.018

DO - 10.1016/j.neurobiolaging.2019.08.018

M3 - Article

C2 - 31585361

AN - SCOPUS:85072756129

VL - 83

SP - 105

EP - 113

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -