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P2‐330: Amyloid‐independent mechanisms of Alzheiemer's disease: The role of APP intracellular domain
Author(s) -
Pimplikar Sanjay,
Ghosal Kaushik,
Fan Qingyuan
Publication year - 2011
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.2011.05.1206
Subject(s) - genetically modified mouse , pathogenesis , amyloid precursor protein , neuroinflammation , presenilin , transgene , neurogenesis , intracellular , amyloid (mycology) , biology , in vivo , amyloid beta , alzheimer's disease , microbiology and biotechnology , endocrinology , disease , medicine , immunology , inflammation , pathology , gene , biochemistry , genetics
cent advances in molecular imaging and the use of different PET ligands for in vivo Ab imaging in AD has opened up a new dimension for further understanding of the complex disease processes occurring during the progression of disease. Longitudinal [C]-PIB PET imaging studies in subjects with mild cognitive impairment and AD have demonstrated that Ab accumulates in the brain early during life. It is suggested that this build-up of Ab in the AD brain triggers a cascade of neurodegenerative events, including inflammatory processes, oxidative stress, neurofibrillary tangles, neuronal network dysfunction with synaptic loss and neurotransmitter deficits leading to cognitive impairment. However, it is not yet clear how the amount and distribution of Aß in brain areas affected by AD is associated with the abovementioned neurodegenerative changes during disease progression. Methods: In the present study, we examined bymeans of quantitative in vitro autoradiography the laminar distributions of fibrillar Ab (H-PIB) and activated astrocytes (H)L-deprenyl) in relation to the distribution of cholinergic nicotinic receptors (H)-nicotine) in the autopsy brain hemisphere of a histopathological confirmed AD patient. Results: Different laminar distribution patterns of fibrillar Ab and activated astrocytes were observed in the various brain regions studied. Brain regions with high fibrillar Ab showed a reduced distribution of neuronal nicotinic receptors confirming a recent observation reported by our group (Kadir et al., 2011. Brain 134:301-317). Conclusions: The different laminar binding patterns for H-PIB andH-L-deprenyl as well as the reduced binding of [H]-nicotine in AD brain regions may reflect different pathological mechanisms during disease progression.