Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation

Kiyoshi Niwa, Linda Younkin, Christine Ebeling, Sherry K. Turner, David Westaway, Steven G Younkin, Karen Hsiao Ashe, George A. Carlson, Costantino Iadecola

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide (Aβ), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Aβ have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Aβ concentration and is reproduced in normal mice by topical neocortical application of exogenous Aβ1-40 but not Aβ1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Aβ1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Aβ overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Aβ-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity.

Original languageEnglish (US)
Pages (from-to)9735-9740
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number17
StatePublished - Aug 15 2000

Fingerprint

Serum Amyloid A Protein
Amyloid beta-Protein Precursor
Neocortex
Hyperemia
Presenilin-1
Somatosensory Cortex
Amyloid
Transgenic Mice
Alzheimer Disease
Glucose
Peptides
Brain

Keywords

  • β-Amyloid
  • Alzheimer's disease
  • Cerebral blood flow
  • Functional activation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. / Niwa, Kiyoshi; Younkin, Linda; Ebeling, Christine; Turner, Sherry K.; Westaway, David; Younkin, Steven G; Ashe, Karen Hsiao; Carlson, George A.; Iadecola, Costantino.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 17, 15.08.2000, p. 9735-9740.

Research output: Contribution to journalArticle

Niwa, K, Younkin, L, Ebeling, C, Turner, SK, Westaway, D, Younkin, SG, Ashe, KH, Carlson, GA & Iadecola, C 2000, 'Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9735-9740.
Niwa, Kiyoshi ; Younkin, Linda ; Ebeling, Christine ; Turner, Sherry K. ; Westaway, David ; Younkin, Steven G ; Ashe, Karen Hsiao ; Carlson, George A. ; Iadecola, Costantino. / Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 17. pp. 9735-9740.
@article{2df313ad908340c8ae7e0da47a62405b,
title = "Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation",
abstract = "Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide (Aβ), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Aβ have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Aβ concentration and is reproduced in normal mice by topical neocortical application of exogenous Aβ1-40 but not Aβ1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Aβ1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Aβ overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Aβ-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity.",
keywords = "β-Amyloid, Alzheimer's disease, Cerebral blood flow, Functional activation",
author = "Kiyoshi Niwa and Linda Younkin and Christine Ebeling and Turner, {Sherry K.} and David Westaway and Younkin, {Steven G} and Ashe, {Karen Hsiao} and Carlson, {George A.} and Costantino Iadecola",
year = "2000",
month = "8",
day = "15",
language = "English (US)",
volume = "97",
pages = "9735--9740",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

TY - JOUR

T1 - Aβ1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation

AU - Niwa, Kiyoshi

AU - Younkin, Linda

AU - Ebeling, Christine

AU - Turner, Sherry K.

AU - Westaway, David

AU - Younkin, Steven G

AU - Ashe, Karen Hsiao

AU - Carlson, George A.

AU - Iadecola, Costantino

PY - 2000/8/15

Y1 - 2000/8/15

N2 - Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide (Aβ), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Aβ have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Aβ concentration and is reproduced in normal mice by topical neocortical application of exogenous Aβ1-40 but not Aβ1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Aβ1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Aβ overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Aβ-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity.

AB - Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide (Aβ), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Aβ have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Aβ concentration and is reproduced in normal mice by topical neocortical application of exogenous Aβ1-40 but not Aβ1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Aβ1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Aβ overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Aβ-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity.

KW - β-Amyloid

KW - Alzheimer's disease

KW - Cerebral blood flow

KW - Functional activation

UR - http://www.scopus.com/inward/record.url?scp=0034662501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034662501&partnerID=8YFLogxK

M3 - Article

VL - 97

SP - 9735

EP - 9740

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -