title: Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.
abstract: Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: C S
authors.initials: CS
authors.lastname: Janota
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Brites
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women׳s Hospital, Harvard Medical School, Boston, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lemere
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: abrito@ff.ulisboa.pt.
authors.forename: M A
authors.initials: MA
authors.lastname: Brito
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000473:pathology / Q000502:physiology*; D020286:Pericytes / Q000473:pathology / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer׳s disease; Blood-brain barrier disruption; Glial activation; Microvasculature; Pericytes; Receptor for advanced glycation endproducts