Dataset Information

Neuronal activity regulates the regional vulnerability to amyloid-? deposition.

ABSTRACT: Amyloid-? (A?) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to A? deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) A?, which drives local A? aggregation. Using in vivo microdialysis, we show that ISF A? concentrations in several brain regions of APP transgenic mice before plaque deposition were commensurate with the degree of subsequent plaque deposition and with the concentration of lactate, a marker of neuronal activity. Furthermore, unilateral vibrissal stimulation increased ISF A?, and unilateral vibrissal deprivation decreased ISF A? and lactate, in contralateral barrel cortex. Long-term unilateral vibrissal deprivation decreased amyloid plaque formation and growth. Our results suggest a mechanism to account for the vulnerability of specific brain regions to A? deposition in Alzheimer's disease.

SUBMITTER: Bero AW

PROVIDER: S-EPMC3102784 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuronal activity regulates the regional vulnerability to amyloid-β deposition.

Bero Adam W AW Yan Ping P Roh Jee Hoon JH Cirrito John R JR Stewart Floy R FR Raichle Marcus E ME Lee Jin-Moo JM Holtzman David M DM

Nature neuroscience 20110501 6

Amyloid-β (Aβ) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to Aβ deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) Aβ, which drives local Aβ aggregation. Using in vivo microdialysis, we show that ISF Aβ concentrations in several brain regions of APP transgenic mice ...[more]

PMID: 21532579

Similar Datasets

Project description:SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B-positive cognitively normal older subjects (T = 10.62, P < 0.001), but, only the Pittsburgh compound B-positive cognitively normal older subjects group showed significantly higher Pittsburgh compound B retention in the highest compared to the lowest glucose metabolism regions defined in young adults (T = 2.05, P < 0.05). Regional differences in age and amyloid-β-dependent changes in glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose metabolism in the precuneus was maintained across the lifespan (right hemisphere: F = 7.69, P < 0.001; left hemisphere: F = 8.69, P < 0.001). Greater Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-β-related increases in glucose metabolism. Our results indicate that although early and life-long regional variation in glucose metabolism relates to the regional vulnerability to amyloid-β accumulation, Alzheimer's disease-related hypometabolism is more specific to brain regions showing age-invariant glucose metabolism and amyloid-β-related hypermetabolism.

Dataset Information

Neuronal activity regulates the regional vulnerability to amyloid-? deposition.

Publications

Neuronal activity regulates the regional vulnerability to amyloid-β deposition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets