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P4‐106: The Pathological Role of TDP‐43 and NF‐KB in Mild Cognitive Impairment and Alzheimer's Disease
Author(s) -
Ohta Yasuyuki,
Tremblay Cyntia,
Schneider Julie A.,
Bennett David A.,
Calon Frederic,
Julien Jean-Pierre,
Abe Koji
Publication year - 2016
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.2016.06.2197
Subject(s) - pathological , episodic memory , neuroscience , pathogenesis , disease , amyotrophic lateral sclerosis , psychology , cognition , alzheimer's disease , medicine
in the brain, thus contributing to the neurodegeneration that characterizes AD. The understanding of host immune system control toward HSV-1 reactivation is only partial. We recently described the presence of a negative correlation between HSV-1 specific antibodies (IgG) titers and cortical grey matter volume in AD patients as evaluated bymagnetic resonance imaging (MRI), suggesting that a strong HSV-1 specific humoral immunity could protect against neurodegeneration (Mancuso et al, Front. Aging Neurosci. 2014). Different IgG subclasses are characterized by different functional properties and activity against antigens. The objective of this study was to analyze HSV-1 specific IgG subclasses in individuals with a diagnosis of either AD or mild cognitive impairment (MCI); results were compared to those obtained in age and sex matched healthy controls (HC). Methods:HSV-1-specific IgG subclasses were evaluated in sera of HSV-1-seropositive AD (n1⁄428), MCI (n1⁄428) and HC (n1⁄4 27) using commercially available ELISA test with subclass-specific monoclonal antisera. Results: HSV-1-specific IgG1 were detected in 100% of AD and MCI subjects and in 85% of HC, with similar levels among examined groups. Interestingly, strong positive correlation between IgG1 and total IgG levels was evidenced in AD (r1⁄40.793, p<0.0001) and in HC (r1⁄40.452; p1⁄40.03), but not in MCI individuals. IgG3antibodies were significantly more frequent in MCI (93%) and HC (74%) than in AD subjects (64%; p1⁄40.02) and their titers were significantly increased as well in HC (OD1⁄40.88; p1⁄40.01) and MCI individuals (OD1⁄40.81; p1⁄40.06) compared to AD (OD1⁄40.67). Conclusions:HSV-1-specific IgG subclasses differ among AD, MCI and HC. IgG1 subtype response is the predominant type of response in AD and HC subjects, but a significant decreased in IgG3 was detected in AD compared to MCI and HC. Further studies are needed to understand the functional significance of the different humoral response observed between AD, MCI and HC.