Specific downregulation of presenilin 2 gene expression is prominent during early stages of sporadic late-onset Alzheimer's disease

Pamela J. McMillan, James B. Leverenz, Daniel Dorsa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mutations in the presenilin genes PS1 and PS2 cause familial Alzheimer's disease (AD). In a previous study, we reported that PS2 mRNA levels are decreased in the hippocampus, frontal cortex and basal forebrain of subjects with late-onset sporadic AD. In this study, we examined whether this downregulation occurs as the disease progresses from mild to severe stages or whether downregulation of PS2 expression is an early event in AD. We used in situ hybridization histochemistry to quantify the level of expression of PS2 message in the hippocampus of normal subjects and subjects with mild, moderate or severe AD. Several regions of the hippocampus which are sequentially susceptible to AD neuropathology as the disease progresses in severity were analyzed. We demonstrate that specific downregulation of PS2 expression is as severe in subjects with mild AD as it is in subjects in late stages of the disease. In addition, we show that hippocampal regions that are relatively free of AD neuropathology during early stages of the disease exhibit severely compromised PS2 mRNA levels even in mild AD cases. In contrast, PS2 is expressed at normal levels in the cerebellum, a region which succumbs to significantly fewer AD-related insults even at very advanced stages of the disease. These results suggest that the specific downregulation of PS2 gene expression is an early event in sporadic late-onset AD. Theme: Disorders of the nervous system. Topic: Degenerative disease: Alzheimer's - other. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
JournalMolecular Brain Research
Volume78
Issue number1-2
DOIs
StatePublished - May 31 2000
Externally publishedYes

Fingerprint

Presenilin-2
Alzheimer Disease
Down-Regulation
Gene Expression
Hippocampus
Presenilins
Messenger RNA
Frontal Lobe
Nervous System Diseases
Cerebellum
In Situ Hybridization

Keywords

  • Alzheimer's disease
  • Cerebellum
  • Gene expression
  • Hippocampus
  • Presenilin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Specific downregulation of presenilin 2 gene expression is prominent during early stages of sporadic late-onset Alzheimer's disease. / McMillan, Pamela J.; Leverenz, James B.; Dorsa, Daniel.

In: Molecular Brain Research, Vol. 78, No. 1-2, 31.05.2000, p. 138-145.

Research output: Contribution to journalArticle

@article{905f5d6b8a94418688fdfe8596cb5567,
title = "Specific downregulation of presenilin 2 gene expression is prominent during early stages of sporadic late-onset Alzheimer's disease",
abstract = "Mutations in the presenilin genes PS1 and PS2 cause familial Alzheimer's disease (AD). In a previous study, we reported that PS2 mRNA levels are decreased in the hippocampus, frontal cortex and basal forebrain of subjects with late-onset sporadic AD. In this study, we examined whether this downregulation occurs as the disease progresses from mild to severe stages or whether downregulation of PS2 expression is an early event in AD. We used in situ hybridization histochemistry to quantify the level of expression of PS2 message in the hippocampus of normal subjects and subjects with mild, moderate or severe AD. Several regions of the hippocampus which are sequentially susceptible to AD neuropathology as the disease progresses in severity were analyzed. We demonstrate that specific downregulation of PS2 expression is as severe in subjects with mild AD as it is in subjects in late stages of the disease. In addition, we show that hippocampal regions that are relatively free of AD neuropathology during early stages of the disease exhibit severely compromised PS2 mRNA levels even in mild AD cases. In contrast, PS2 is expressed at normal levels in the cerebellum, a region which succumbs to significantly fewer AD-related insults even at very advanced stages of the disease. These results suggest that the specific downregulation of PS2 gene expression is an early event in sporadic late-onset AD. Theme: Disorders of the nervous system. Topic: Degenerative disease: Alzheimer's - other. Copyright (C) 2000 Elsevier Science B.V.",
keywords = "Alzheimer's disease, Cerebellum, Gene expression, Hippocampus, Presenilin",
author = "McMillan, {Pamela J.} and Leverenz, {James B.} and Daniel Dorsa",
year = "2000",
month = "5",
day = "31",
doi = "10.1016/S0169-328X(00)00086-3",
language = "English (US)",
volume = "78",
pages = "138--145",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Specific downregulation of presenilin 2 gene expression is prominent during early stages of sporadic late-onset Alzheimer's disease

AU - McMillan, Pamela J.

AU - Leverenz, James B.

AU - Dorsa, Daniel

PY - 2000/5/31

Y1 - 2000/5/31

N2 - Mutations in the presenilin genes PS1 and PS2 cause familial Alzheimer's disease (AD). In a previous study, we reported that PS2 mRNA levels are decreased in the hippocampus, frontal cortex and basal forebrain of subjects with late-onset sporadic AD. In this study, we examined whether this downregulation occurs as the disease progresses from mild to severe stages or whether downregulation of PS2 expression is an early event in AD. We used in situ hybridization histochemistry to quantify the level of expression of PS2 message in the hippocampus of normal subjects and subjects with mild, moderate or severe AD. Several regions of the hippocampus which are sequentially susceptible to AD neuropathology as the disease progresses in severity were analyzed. We demonstrate that specific downregulation of PS2 expression is as severe in subjects with mild AD as it is in subjects in late stages of the disease. In addition, we show that hippocampal regions that are relatively free of AD neuropathology during early stages of the disease exhibit severely compromised PS2 mRNA levels even in mild AD cases. In contrast, PS2 is expressed at normal levels in the cerebellum, a region which succumbs to significantly fewer AD-related insults even at very advanced stages of the disease. These results suggest that the specific downregulation of PS2 gene expression is an early event in sporadic late-onset AD. Theme: Disorders of the nervous system. Topic: Degenerative disease: Alzheimer's - other. Copyright (C) 2000 Elsevier Science B.V.

AB - Mutations in the presenilin genes PS1 and PS2 cause familial Alzheimer's disease (AD). In a previous study, we reported that PS2 mRNA levels are decreased in the hippocampus, frontal cortex and basal forebrain of subjects with late-onset sporadic AD. In this study, we examined whether this downregulation occurs as the disease progresses from mild to severe stages or whether downregulation of PS2 expression is an early event in AD. We used in situ hybridization histochemistry to quantify the level of expression of PS2 message in the hippocampus of normal subjects and subjects with mild, moderate or severe AD. Several regions of the hippocampus which are sequentially susceptible to AD neuropathology as the disease progresses in severity were analyzed. We demonstrate that specific downregulation of PS2 expression is as severe in subjects with mild AD as it is in subjects in late stages of the disease. In addition, we show that hippocampal regions that are relatively free of AD neuropathology during early stages of the disease exhibit severely compromised PS2 mRNA levels even in mild AD cases. In contrast, PS2 is expressed at normal levels in the cerebellum, a region which succumbs to significantly fewer AD-related insults even at very advanced stages of the disease. These results suggest that the specific downregulation of PS2 gene expression is an early event in sporadic late-onset AD. Theme: Disorders of the nervous system. Topic: Degenerative disease: Alzheimer's - other. Copyright (C) 2000 Elsevier Science B.V.

KW - Alzheimer's disease

KW - Cerebellum

KW - Gene expression

KW - Hippocampus

KW - Presenilin

UR - http://www.scopus.com/inward/record.url?scp=0034737987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034737987&partnerID=8YFLogxK

U2 - 10.1016/S0169-328X(00)00086-3

DO - 10.1016/S0169-328X(00)00086-3

M3 - Article

C2 - 10891593

AN - SCOPUS:0034737987

VL - 78

SP - 138

EP - 145

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -