Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

TitleAdipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.
Publication TypeJournal Article
Year of Publication2016
AuthorsIshii M, Iadecola C
JournalBiochim Biophys Acta
Volume1862
Issue5
Pagination966-74
Date Published2016 May
ISSN0006-3002
Abstract

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

DOI10.1016/j.bbadis.2015.10.029
Alternate JournalBiochim. Biophys. Acta
PubMed ID26546479
PubMed Central IDPMC4821723
Grant ListK08 AG051179 / AG / NIA NIH HHS / United States
R01 NS037853 / NS / NINDS NIH HHS / United States