Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease

Stephen D. Ginsberg, Elliott J. Mufson, Melissa J. Alldred, Scott E. Counts, Joanne Wuu, Ralph A. Nixon, Shaoli Che

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Endocytic system dysfunction is one of the earliest disturbances that occur in Alzheimer's disease (AD), and may underlie the selective vulnerability of cholinergic basal forebrain (CBF) neurons during the progression of dementia. Herein we report that genes regulating early and late endosomes are selectively upregulated within CBF neurons in mild cognitive impairment (MCI) and AD. Specifically, upregulation of rab4, rab5, rab7, and rab27 was observed in CBF neurons microdissected from postmortem brains of individuals with MCI and AD compared to age-matched control subjects with no cognitive impairment (NCI). Upregulated expression of rab4, rab5, rab7, and rab27 correlated with antemortem measures of cognitive decline in individuals with MCI and AD. qPCR validated upregulation of these select rab GTPases within microdissected samples of the basal forebrain. Moreover, quantitative immunoblot analysis demonstrated upregulation of rab5 protein expression in the basal forebrain of subjects with MCI and AD. The elevation of rab4, rab5, and rab7 expression is consistent with our recent observations in CA1 pyramidal neurons in MCI and AD. These findings provide further support that endosomal pathology accelerates endocytosis and endosome recycling, which may promote aberrant endosomal signaling and neurodegeneration throughout the progression of AD.

Original languageEnglish
Pages (from-to)102-110
Number of pages9
JournalJournal of Chemical Neuroanatomy
Volume42
Issue number2
DOIs
StatePublished - Oct 1 2011

Fingerprint

rab GTP-Binding Proteins
Cholinergic Agents
Alzheimer Disease
Up-Regulation
Neurons
Endosomes
rab5 GTP-Binding Proteins
Pyramidal Cells
Endocytosis
Cognitive Dysfunction
Basal Forebrain
Dementia
Pathology
Brain

Keywords

  • Cognitive decline
  • Endosome
  • Microarray
  • Mild cognitive impairment
  • QPCR
  • Rab5

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease. / Ginsberg, Stephen D.; Mufson, Elliott J.; Alldred, Melissa J.; Counts, Scott E.; Wuu, Joanne; Nixon, Ralph A.; Che, Shaoli.

In: Journal of Chemical Neuroanatomy, Vol. 42, No. 2, 01.10.2011, p. 102-110.

Research output: Contribution to journalArticle

Ginsberg, Stephen D. ; Mufson, Elliott J. ; Alldred, Melissa J. ; Counts, Scott E. ; Wuu, Joanne ; Nixon, Ralph A. ; Che, Shaoli. / Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease. In: Journal of Chemical Neuroanatomy. 2011 ; Vol. 42, No. 2. pp. 102-110.
@article{1b43b42bfa5a44c2a775400fe49dbce7,
title = "Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease",
abstract = "Endocytic system dysfunction is one of the earliest disturbances that occur in Alzheimer's disease (AD), and may underlie the selective vulnerability of cholinergic basal forebrain (CBF) neurons during the progression of dementia. Herein we report that genes regulating early and late endosomes are selectively upregulated within CBF neurons in mild cognitive impairment (MCI) and AD. Specifically, upregulation of rab4, rab5, rab7, and rab27 was observed in CBF neurons microdissected from postmortem brains of individuals with MCI and AD compared to age-matched control subjects with no cognitive impairment (NCI). Upregulated expression of rab4, rab5, rab7, and rab27 correlated with antemortem measures of cognitive decline in individuals with MCI and AD. qPCR validated upregulation of these select rab GTPases within microdissected samples of the basal forebrain. Moreover, quantitative immunoblot analysis demonstrated upregulation of rab5 protein expression in the basal forebrain of subjects with MCI and AD. The elevation of rab4, rab5, and rab7 expression is consistent with our recent observations in CA1 pyramidal neurons in MCI and AD. These findings provide further support that endosomal pathology accelerates endocytosis and endosome recycling, which may promote aberrant endosomal signaling and neurodegeneration throughout the progression of AD.",
keywords = "Cognitive decline, Endosome, Microarray, Mild cognitive impairment, QPCR, Rab5",
author = "Ginsberg, {Stephen D.} and Mufson, {Elliott J.} and Alldred, {Melissa J.} and Counts, {Scott E.} and Joanne Wuu and Nixon, {Ralph A.} and Shaoli Che",
year = "2011",
month = "10",
day = "1",
doi = "10.1016/j.jchemneu.2011.05.012",
language = "English",
volume = "42",
pages = "102--110",
journal = "Journal of Chemical Neuroanatomy",
issn = "0891-0618",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease

AU - Ginsberg, Stephen D.

AU - Mufson, Elliott J.

AU - Alldred, Melissa J.

AU - Counts, Scott E.

AU - Wuu, Joanne

AU - Nixon, Ralph A.

AU - Che, Shaoli

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Endocytic system dysfunction is one of the earliest disturbances that occur in Alzheimer's disease (AD), and may underlie the selective vulnerability of cholinergic basal forebrain (CBF) neurons during the progression of dementia. Herein we report that genes regulating early and late endosomes are selectively upregulated within CBF neurons in mild cognitive impairment (MCI) and AD. Specifically, upregulation of rab4, rab5, rab7, and rab27 was observed in CBF neurons microdissected from postmortem brains of individuals with MCI and AD compared to age-matched control subjects with no cognitive impairment (NCI). Upregulated expression of rab4, rab5, rab7, and rab27 correlated with antemortem measures of cognitive decline in individuals with MCI and AD. qPCR validated upregulation of these select rab GTPases within microdissected samples of the basal forebrain. Moreover, quantitative immunoblot analysis demonstrated upregulation of rab5 protein expression in the basal forebrain of subjects with MCI and AD. The elevation of rab4, rab5, and rab7 expression is consistent with our recent observations in CA1 pyramidal neurons in MCI and AD. These findings provide further support that endosomal pathology accelerates endocytosis and endosome recycling, which may promote aberrant endosomal signaling and neurodegeneration throughout the progression of AD.

AB - Endocytic system dysfunction is one of the earliest disturbances that occur in Alzheimer's disease (AD), and may underlie the selective vulnerability of cholinergic basal forebrain (CBF) neurons during the progression of dementia. Herein we report that genes regulating early and late endosomes are selectively upregulated within CBF neurons in mild cognitive impairment (MCI) and AD. Specifically, upregulation of rab4, rab5, rab7, and rab27 was observed in CBF neurons microdissected from postmortem brains of individuals with MCI and AD compared to age-matched control subjects with no cognitive impairment (NCI). Upregulated expression of rab4, rab5, rab7, and rab27 correlated with antemortem measures of cognitive decline in individuals with MCI and AD. qPCR validated upregulation of these select rab GTPases within microdissected samples of the basal forebrain. Moreover, quantitative immunoblot analysis demonstrated upregulation of rab5 protein expression in the basal forebrain of subjects with MCI and AD. The elevation of rab4, rab5, and rab7 expression is consistent with our recent observations in CA1 pyramidal neurons in MCI and AD. These findings provide further support that endosomal pathology accelerates endocytosis and endosome recycling, which may promote aberrant endosomal signaling and neurodegeneration throughout the progression of AD.

KW - Cognitive decline

KW - Endosome

KW - Microarray

KW - Mild cognitive impairment

KW - QPCR

KW - Rab5

UR - http://www.scopus.com/inward/record.url?scp=80052102358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052102358&partnerID=8YFLogxK

U2 - 10.1016/j.jchemneu.2011.05.012

DO - 10.1016/j.jchemneu.2011.05.012

M3 - Article

VL - 42

SP - 102

EP - 110

JO - Journal of Chemical Neuroanatomy

JF - Journal of Chemical Neuroanatomy

SN - 0891-0618

IS - 2

ER -