Premium
P2‐417: GAD65, GAD67 and GABAT immunoreactivity in human brain and GAD65 loss in Alzheimer's disease
Author(s) -
Schwab Claudia,
Yu Sheng,
Wong Winnie,
McGeer Edie,
McGeer Patrick
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.2042
Subject(s) - neuropil , glutamate decarboxylase , gabaergic , synaptophysin , biology , neuroscience , hippocampus , human brain , cerebellum , neocortex , glutamate receptor , cerebral cortex , immunohistochemistry , central nervous system , pathology , inhibitory postsynaptic potential , enzyme , medicine , biochemistry , immunology , receptor
genesis. Based on such findings, we were prompted to develop a next-generation model of the disease using transgenic rat technology.Methods:We developed a transgenic rat model on a Fischer 344 background (line TgF344-AD) based on over-expression of mutant human amyloid precursor protein and mutant human presenilin-1, each independent and dominant causes of familial early-onset AD. We applied histopathological, ultrastructural, and biochemical techniques to characterize this Tg rat model. Markers of neural stem cell differentiation into neurons were used to track neurogenesis throughout the course of neural development and into adulthood. Results: Tg rats faithfully recapitulate the hallmarks of AD age-dependent cerebral amyloidosis, tauopathy (including neurofibrillary tangles), gliosis, andmost notably widespread apoptotic loss of neurons in the cerebral cortex and hippocampus leading to cognitive deficits. Results show age-dependent dysfunction within the neurogenic niche of this novel transgenic AD rat model, beginning prior to the appearance of frank AD-like pathology. Specifically, there is a cumulative decline in doublecortin and Tuj1 double-positive neural progenitors in TgF344-AD rats.Conclusions:Given the inverse relationship between adult neurogenesis and AD-like pathology in mouse models, these results add to a growing body of data pointing to aberrant adult neurogenesis in the context of AD.