title: Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice.
abstract: Cerebral microvascular amyloid beta protein (Abeta) deposition and associated neuroinflammation are increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease and related cerebral amyloid angiopathy (CAA) disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Abeta precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits exhibiting robust neuroinflammation. In the present study, we sought to determine if the unique amyloid pathology of Tg-SwDI mice was associated with deficits in behavioral performance. Behavioral performance tests that assessed a variety of psychological functions, including overall activity, motor ability, balance and strength, anxiety, impulsivity, and learning were conducted on homozygous Tg-SwDI mice and similarly aged wild-type C57Bl/6 mice. Our results indicate that Tg-SwDI mice were impaired in the performance of the Barnes maze learning and memory task at 3, 9, and 12 months of age. While more widespread cerebral microvascular Abeta pathology was evident in older animals, the evaluation of the Abeta pathology in the 3 months old transgenic animals revealed specific accumulation of microvascular amyloid and markedly elevated numbers of reactive astrocytes and activated microglia restricted to the subiculum. These findings indicate that early-onset accumulation of subicular microvascular amyloid and accompanying neuroinflammation correlates with impaired performance in the learning and memory task in Tg-SwDI mice.
authors.affiliation: Department of Medicine, Health Sciences Center T-15/083, Stony Brook University, Stony Brook, NY 11794-8153, USA.
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: A M
authors.initials: AM
authors.lastname: Grande
authors.forename: J K
authors.initials: JK
authors.lastname: Robinson
authors.forename: M L
authors.initials: ML
authors.lastname: Previti
authors.forename: M
authors.initials: M
authors.lastname: Vasek
authors.forename: J
authors.initials: J
authors.lastname: Davis
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation / Q000503:physiopathology; D017628:Microglia / Q000473:pathology; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor