Dataset Information

Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease.

ABSTRACT: Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and IBA1(+) and CD68(+) activated microglia in randomly selected dense-core (Thioflavin-S(+)) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques. Dystrophic neurites (Kendall ? = 0.34, P = 0.001), reactive astrocytes (Kendall ? = 0.30, P = 0.003), and CD68(+) (Kendall ? = 0.48, P < 0.0001), but not IBA1 microglia (Kendall ? = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration. When excluding control subjects, only the positive association between CD68(+) microglia and symptom duration remained significant (Kendall ? = 0.39, P = 0.0003). The presence of the APOE?4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline.

SUBMITTER: Serrano-Pozo A

PROVIDER: S-EPMC4729270 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease.

Serrano-Pozo Alberto A Betensky Rebecca A RA Frosch Matthew P MP Hyman Bradley T BT

The American journal of pathology 20151211 2

Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and I ...[more]

PMID: 26687817

Similar Datasets

Project description:BACKGROUND/OBJECTIVES:Population-based incidence estimates of dementia and Alzheimer disease (AD) provide important information for public health policy and resource allocation. We conducted a meta-analysis of published studies that reported age-specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time. DESIGN:PubMed and MEDLINE were searched for publications through June 30, 2017, using key words "dementia", "Alzheimer", and "incidence." Inclusion criteria for the meta-analysis are: (1) population-based studies using personal interviews and direct examinations of the study subjects, (2) standardized clinical diagnosis criteria, (3) reporting age-specific incidence rates, (4) published in English, and (5) sample size of 500 or greater and length of follow-up of 2 years or greater. Mixed-effects models were used to determine the association between birth year and incidence rates. MEASUREMENTS:Age-specific dementia/AD incidence rates and their standard errors reported in each study. RESULTS:Thirty-eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65-74, 75-84, and 85 years and older). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups, while studies in non-Western countries showed significantly increased AD incidence rates for the 65 to 74 years age group (odds ratio = 2.78; P =?.04), but a nonsignificant association for the 75 to 84 or 85 years and older groups. CONCLUSION:Dementia incidence declined over the past four decades, but AD incidence did not decline. Further research, especially from non-Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.

Dataset Information

Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease.

Publications

Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets