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 language | English |
|---|---|
| Pages (from-to) | 102-110 |
| Number of pages | 9 |
| Journal | Journal of Chemical Neuroanatomy |
| Volume | 42 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 1 2011 |
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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 journal › Article
}
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 -