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P1‐212: Distribution of β‐amyloid deposition and its clinical relevance in dementia with Lewy bodies: A pathological study
Author(s) -
Fujishiro Hiroshige,
Iseki Eizo,
Higashi Shinji,
Kasanuki Koji,
Yamamoto Ryoko,
Togo Takashi,
Katsuse Omi,
Uchikado Hirotake,
Kosaka Kenji,
Arai Heii,
Sato Kiyoshi
Publication year - 2010
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.2010.05.763
Subject(s) - dementia with lewy bodies , pathology , pathological , dementia , amyloid (mycology) , medicine , alzheimer's disease , lewy body , neurofibrillary tangle , clinical significance , psychology , neuroscience , disease , senile plaques
the PI3-family kinases, ATM and ATR. After DNA damage, ATM autophosophorylates on serine1981, activating the kinase; ATR is also phosphorylated. Downstream targets of ATM include Chk2, a cell cycle checkpoint kinase. Methods: Immunohistochemistry was performed on brain sections of hippocampus and cerebellum obtained from AD and age-matched control subjects. TUNEL was used to directly document the presence of DNA damage. Results: Phosphorylated ATM, ATR and Chk2 (ATM*, ATR*, Chk2*) were detected in both large and small hippocampal and cerebellar neurons, and the extent of the labeling correlated well with the diagnosis of AD. When found in the nucleus, their presence correlated well with the TUNEL reaction. Surprisingly, ATM*, ATR* and Ch2* were also found in the cytoplasm in some cell populations, where their presence was poorly correlated with TUNEL-labeled nuclei. The nature of the cytoplasmic labeling varied significantly among the cell types. In cerebellar Purkinje cells, for example, ATM* was found distributed throughout the cell soma and thicker dendritic branches. By contrast, in hippocampal pyramidal cells, ATM*, ATR* and Ch2* were found in dense granules that labeled with granulovacuolar degeneration (GVD) markers. GVD localization was not observed for either 53BP1 or gH2AX, two DNA binding proteins associated with DNA damage. A significant proportion of the ATM*/ATR*/Ch2*-positive GVD granules were also positively stained by the phospho-tau marker AT8 and the autophagosome marker, LC3-II. Conclusions: As DNA damage is restricted to the cell nucleus, we suggest that the activation of the response proteins likely precedes and may help to initiate the formation of GVD granules.