Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-β1 transgenic mice and functional metabolic correlates

T. Wyss-Coray, L. Lin, D. Von Euw, E. Masliah, L. Mucke, P. Lacombe

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is frequently associated with cerebrovascular changes, including perivascular astrocytosis, amyloid deposition, and microvascular degeneration, but it is not known whether these pathological changes contribute to functional deficits in AD. To characterize the temporal relationship between amyloid deposition, cerebrovascular abnormalities, and potential functional changes, we studied transgenic mice that express transforming growth factor-β1 (TGF-β1) at low levels in astrocytes. TGF-β1 induced a prominent perivascular astrocytosis, followed by the accumulation of basement membrane proteins in microvessels, thickening of capillary basement membranes, and later, around 6 months of age, deposition of amyloid in cerebral blood vessels. At 9 months of age, various AD-like degenerative alterations were observed in endothelial cells and pericytes. Associated with these morphological changes were changes in regional cerebral glucose utilization. Preliminary results showed that TGF-β1 mice had significantly decreased glucose utilization in the mammillary bodies, structures involved in mnemonic and learning processes. Glucose utilization tended to be decreased in several other brain regions as well; however, in the inferior colliculus, it was markedly higher in TGF-β1 mice than in controls. We conclude that chronic overproduction of TGF-β1 triggers a pathogenic cascade leading to AD-like cerebrovascular amyloidosis, microvascular degeneration, and local alterations in brain metabolic activity. Similar mechanisms may be involved in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume903
StatePublished - 2000
Externally publishedYes

Fingerprint

Transforming Growth Factors
Pathology
Transgenic Mice
Alzheimer Disease
Amyloid
Gliosis
Basement Membrane
Glucose
Brain
Mammillary Bodies
Inferior Colliculi
Pericytes
Endothelial cells
Blood vessels
Amyloidosis
Microvessels
Astrocytes
Blood Vessels
Membrane Proteins
Endothelial Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-β1 transgenic mice and functional metabolic correlates. / Wyss-Coray, T.; Lin, L.; Von Euw, D.; Masliah, E.; Mucke, L.; Lacombe, P.

In: Annals of the New York Academy of Sciences, Vol. 903, 2000, p. 317-323.

Research output: Contribution to journalArticle

@article{c95e06dc89644d8f8113a43cd4b0de94,
title = "Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-β1 transgenic mice and functional metabolic correlates",
abstract = "Alzheimer's disease (AD) is frequently associated with cerebrovascular changes, including perivascular astrocytosis, amyloid deposition, and microvascular degeneration, but it is not known whether these pathological changes contribute to functional deficits in AD. To characterize the temporal relationship between amyloid deposition, cerebrovascular abnormalities, and potential functional changes, we studied transgenic mice that express transforming growth factor-β1 (TGF-β1) at low levels in astrocytes. TGF-β1 induced a prominent perivascular astrocytosis, followed by the accumulation of basement membrane proteins in microvessels, thickening of capillary basement membranes, and later, around 6 months of age, deposition of amyloid in cerebral blood vessels. At 9 months of age, various AD-like degenerative alterations were observed in endothelial cells and pericytes. Associated with these morphological changes were changes in regional cerebral glucose utilization. Preliminary results showed that TGF-β1 mice had significantly decreased glucose utilization in the mammillary bodies, structures involved in mnemonic and learning processes. Glucose utilization tended to be decreased in several other brain regions as well; however, in the inferior colliculus, it was markedly higher in TGF-β1 mice than in controls. We conclude that chronic overproduction of TGF-β1 triggers a pathogenic cascade leading to AD-like cerebrovascular amyloidosis, microvascular degeneration, and local alterations in brain metabolic activity. Similar mechanisms may be involved in AD pathogenesis.",
author = "T. Wyss-Coray and L. Lin and {Von Euw}, D. and E. Masliah and L. Mucke and P. Lacombe",
year = "2000",
language = "English (US)",
volume = "903",
pages = "317--323",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-β1 transgenic mice and functional metabolic correlates

AU - Wyss-Coray, T.

AU - Lin, L.

AU - Von Euw, D.

AU - Masliah, E.

AU - Mucke, L.

AU - Lacombe, P.

PY - 2000

Y1 - 2000

N2 - Alzheimer's disease (AD) is frequently associated with cerebrovascular changes, including perivascular astrocytosis, amyloid deposition, and microvascular degeneration, but it is not known whether these pathological changes contribute to functional deficits in AD. To characterize the temporal relationship between amyloid deposition, cerebrovascular abnormalities, and potential functional changes, we studied transgenic mice that express transforming growth factor-β1 (TGF-β1) at low levels in astrocytes. TGF-β1 induced a prominent perivascular astrocytosis, followed by the accumulation of basement membrane proteins in microvessels, thickening of capillary basement membranes, and later, around 6 months of age, deposition of amyloid in cerebral blood vessels. At 9 months of age, various AD-like degenerative alterations were observed in endothelial cells and pericytes. Associated with these morphological changes were changes in regional cerebral glucose utilization. Preliminary results showed that TGF-β1 mice had significantly decreased glucose utilization in the mammillary bodies, structures involved in mnemonic and learning processes. Glucose utilization tended to be decreased in several other brain regions as well; however, in the inferior colliculus, it was markedly higher in TGF-β1 mice than in controls. We conclude that chronic overproduction of TGF-β1 triggers a pathogenic cascade leading to AD-like cerebrovascular amyloidosis, microvascular degeneration, and local alterations in brain metabolic activity. Similar mechanisms may be involved in AD pathogenesis.

AB - Alzheimer's disease (AD) is frequently associated with cerebrovascular changes, including perivascular astrocytosis, amyloid deposition, and microvascular degeneration, but it is not known whether these pathological changes contribute to functional deficits in AD. To characterize the temporal relationship between amyloid deposition, cerebrovascular abnormalities, and potential functional changes, we studied transgenic mice that express transforming growth factor-β1 (TGF-β1) at low levels in astrocytes. TGF-β1 induced a prominent perivascular astrocytosis, followed by the accumulation of basement membrane proteins in microvessels, thickening of capillary basement membranes, and later, around 6 months of age, deposition of amyloid in cerebral blood vessels. At 9 months of age, various AD-like degenerative alterations were observed in endothelial cells and pericytes. Associated with these morphological changes were changes in regional cerebral glucose utilization. Preliminary results showed that TGF-β1 mice had significantly decreased glucose utilization in the mammillary bodies, structures involved in mnemonic and learning processes. Glucose utilization tended to be decreased in several other brain regions as well; however, in the inferior colliculus, it was markedly higher in TGF-β1 mice than in controls. We conclude that chronic overproduction of TGF-β1 triggers a pathogenic cascade leading to AD-like cerebrovascular amyloidosis, microvascular degeneration, and local alterations in brain metabolic activity. Similar mechanisms may be involved in AD pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0034103604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034103604&partnerID=8YFLogxK

M3 - Article

C2 - 10818521

AN - SCOPUS:0034103604

VL - 903

SP - 317

EP - 323

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -