Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions

Qubai Hu, Lee-Way Jin, Marilyn Y. Starbuck, George M. Martin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

FE65 is a key 'adapter' protein that links a multiprotein complex to an intracellular domain of β-amyloid precursor protein (βPP). Its overexpression modulates the trafficking of βPP and facilitates the generation of β-amyloid (Aβ). FE65 is predominantly expressed in brain tissues. An exon 9-inclusive isoform is exclusively expressed in neurons, and an exon 9-exclusive isoform is only expressed in non-neuronal cells. We quantitated the two isoforms in middle temporal cortex, middle frontal cortex, cerebellar cortex and caudate nucleus of 17 Alzheimer disease (AD) patients, 12 normal controls and 9 non-AD neurodegenerative disease controls by reverse transcription-competitive polymerase chain reaction (RT-cPCR). Expression of the two isoforms was significantly and differentially altered, with a 30-57% decrease in levels of the neuronal form (P < 0.05-0.002) and a 73-135% increase in levels of non-neuronal form (P < 0.02-0.001), in the temporal and frontal cortex of AD brains. These alterations presumably reflect advanced neurodegenerative processes of these regions. Surprisingly, expression of both isoforms was significantly up-regulated by 42-66% in the cerebellar cortex and caudate nucleus of AD brains when compared to normal brains (P < 0.05-0.005). Diffuse Aβ-positive plaques were observed in the cerebellum of these AD subjects but not in the normal controls. Selective up- regulation of only the FE65 neuronal isoform was seen in the cerebellar cortex in association with other neurodegenerative diseases (largely Parkinson's disease). Because FE65 modulates trafficking of βPP toward the production of Aβ, the up-regulation of FE65 in AD cerebellum may be relevant to the genesis of diffuse plaques. Thus, early biochemical alterations in AD, not complicated by advanced pathology, may be beneficially investigated in the less-affected regions of the brain, such as the cerebellum. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)73-86
Number of pages14
JournalJournal of Neuroscience Research
Volume60
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

RNA Isoforms
Cerebellum
Protein Isoforms
Alzheimer Disease
Cerebellar Cortex
Brain
Cerebellar Nuclei
Protein Precursors
Caudate Nucleus
Frontal Lobe
Protein Transport
Temporal Lobe
Neurodegenerative Diseases
Exons
Up-Regulation
Cerebellar Diseases
Multiprotein Complexes
Amyloid beta-Protein Precursor
Amyloid
Reverse Transcription

Keywords

  • Alzheimer disease
  • Cerebellum
  • Diffuse plaques
  • FE65
  • Quantitative RT-PCR

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions. / Hu, Qubai; Jin, Lee-Way; Starbuck, Marilyn Y.; Martin, George M.

In: Journal of Neuroscience Research, Vol. 60, No. 1, 2000, p. 73-86.

Research output: Contribution to journalArticle

@article{ab61611848fc4fc69e3a50f1b306e983,
title = "Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions",
abstract = "FE65 is a key 'adapter' protein that links a multiprotein complex to an intracellular domain of β-amyloid precursor protein (βPP). Its overexpression modulates the trafficking of βPP and facilitates the generation of β-amyloid (Aβ). FE65 is predominantly expressed in brain tissues. An exon 9-inclusive isoform is exclusively expressed in neurons, and an exon 9-exclusive isoform is only expressed in non-neuronal cells. We quantitated the two isoforms in middle temporal cortex, middle frontal cortex, cerebellar cortex and caudate nucleus of 17 Alzheimer disease (AD) patients, 12 normal controls and 9 non-AD neurodegenerative disease controls by reverse transcription-competitive polymerase chain reaction (RT-cPCR). Expression of the two isoforms was significantly and differentially altered, with a 30-57{\%} decrease in levels of the neuronal form (P < 0.05-0.002) and a 73-135{\%} increase in levels of non-neuronal form (P < 0.02-0.001), in the temporal and frontal cortex of AD brains. These alterations presumably reflect advanced neurodegenerative processes of these regions. Surprisingly, expression of both isoforms was significantly up-regulated by 42-66{\%} in the cerebellar cortex and caudate nucleus of AD brains when compared to normal brains (P < 0.05-0.005). Diffuse Aβ-positive plaques were observed in the cerebellum of these AD subjects but not in the normal controls. Selective up- regulation of only the FE65 neuronal isoform was seen in the cerebellar cortex in association with other neurodegenerative diseases (largely Parkinson's disease). Because FE65 modulates trafficking of βPP toward the production of Aβ, the up-regulation of FE65 in AD cerebellum may be relevant to the genesis of diffuse plaques. Thus, early biochemical alterations in AD, not complicated by advanced pathology, may be beneficially investigated in the less-affected regions of the brain, such as the cerebellum. (C) 2000 Wiley-Liss, Inc.",
keywords = "Alzheimer disease, Cerebellum, Diffuse plaques, FE65, Quantitative RT-PCR",
author = "Qubai Hu and Lee-Way Jin and Starbuck, {Marilyn Y.} and Martin, {George M.}",
year = "2000",
doi = "10.1002/(SICI)1097-4547(20000401)60:1<73::AID-JNR8>3.0.CO;2-S",
language = "English (US)",
volume = "60",
pages = "73--86",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions

AU - Hu, Qubai

AU - Jin, Lee-Way

AU - Starbuck, Marilyn Y.

AU - Martin, George M.

PY - 2000

Y1 - 2000

N2 - FE65 is a key 'adapter' protein that links a multiprotein complex to an intracellular domain of β-amyloid precursor protein (βPP). Its overexpression modulates the trafficking of βPP and facilitates the generation of β-amyloid (Aβ). FE65 is predominantly expressed in brain tissues. An exon 9-inclusive isoform is exclusively expressed in neurons, and an exon 9-exclusive isoform is only expressed in non-neuronal cells. We quantitated the two isoforms in middle temporal cortex, middle frontal cortex, cerebellar cortex and caudate nucleus of 17 Alzheimer disease (AD) patients, 12 normal controls and 9 non-AD neurodegenerative disease controls by reverse transcription-competitive polymerase chain reaction (RT-cPCR). Expression of the two isoforms was significantly and differentially altered, with a 30-57% decrease in levels of the neuronal form (P < 0.05-0.002) and a 73-135% increase in levels of non-neuronal form (P < 0.02-0.001), in the temporal and frontal cortex of AD brains. These alterations presumably reflect advanced neurodegenerative processes of these regions. Surprisingly, expression of both isoforms was significantly up-regulated by 42-66% in the cerebellar cortex and caudate nucleus of AD brains when compared to normal brains (P < 0.05-0.005). Diffuse Aβ-positive plaques were observed in the cerebellum of these AD subjects but not in the normal controls. Selective up- regulation of only the FE65 neuronal isoform was seen in the cerebellar cortex in association with other neurodegenerative diseases (largely Parkinson's disease). Because FE65 modulates trafficking of βPP toward the production of Aβ, the up-regulation of FE65 in AD cerebellum may be relevant to the genesis of diffuse plaques. Thus, early biochemical alterations in AD, not complicated by advanced pathology, may be beneficially investigated in the less-affected regions of the brain, such as the cerebellum. (C) 2000 Wiley-Liss, Inc.

AB - FE65 is a key 'adapter' protein that links a multiprotein complex to an intracellular domain of β-amyloid precursor protein (βPP). Its overexpression modulates the trafficking of βPP and facilitates the generation of β-amyloid (Aβ). FE65 is predominantly expressed in brain tissues. An exon 9-inclusive isoform is exclusively expressed in neurons, and an exon 9-exclusive isoform is only expressed in non-neuronal cells. We quantitated the two isoforms in middle temporal cortex, middle frontal cortex, cerebellar cortex and caudate nucleus of 17 Alzheimer disease (AD) patients, 12 normal controls and 9 non-AD neurodegenerative disease controls by reverse transcription-competitive polymerase chain reaction (RT-cPCR). Expression of the two isoforms was significantly and differentially altered, with a 30-57% decrease in levels of the neuronal form (P < 0.05-0.002) and a 73-135% increase in levels of non-neuronal form (P < 0.02-0.001), in the temporal and frontal cortex of AD brains. These alterations presumably reflect advanced neurodegenerative processes of these regions. Surprisingly, expression of both isoforms was significantly up-regulated by 42-66% in the cerebellar cortex and caudate nucleus of AD brains when compared to normal brains (P < 0.05-0.005). Diffuse Aβ-positive plaques were observed in the cerebellum of these AD subjects but not in the normal controls. Selective up- regulation of only the FE65 neuronal isoform was seen in the cerebellar cortex in association with other neurodegenerative diseases (largely Parkinson's disease). Because FE65 modulates trafficking of βPP toward the production of Aβ, the up-regulation of FE65 in AD cerebellum may be relevant to the genesis of diffuse plaques. Thus, early biochemical alterations in AD, not complicated by advanced pathology, may be beneficially investigated in the less-affected regions of the brain, such as the cerebellum. (C) 2000 Wiley-Liss, Inc.

KW - Alzheimer disease

KW - Cerebellum

KW - Diffuse plaques

KW - FE65

KW - Quantitative RT-PCR

UR - http://www.scopus.com/inward/record.url?scp=0034123008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034123008&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4547(20000401)60:1<73::AID-JNR8>3.0.CO;2-S

DO - 10.1002/(SICI)1097-4547(20000401)60:1<73::AID-JNR8>3.0.CO;2-S

M3 - Article

C2 - 10723070

AN - SCOPUS:0034123008

VL - 60

SP - 73

EP - 86

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 1

ER -