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P1‐082: INCREASED GAMMA‐SECRETASE ACTIVITY IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS PATIENTS WITH B‐AMYLOID PATHOLOGY
Author(s) -
Laiterä Tiina,
Sarajärvi Timo,
Haapasalo Annakaisa,
Puli Lakshman Kumar,
Kauppinen Tarja,
Mäkinen Petra,
Rauramaa Tuomas,
Tanila Heikki,
Jääskeläinen Juha E.,
Alafuzoff Irina,
Soininen Hilkka,
Lein Ville,
Hiltunen Mikko
Publication year - 2014
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.2014.05.318
Subject(s) - pathology , medicine , temporal cortex , alzheimer's disease , disease , neuroscience , biology
Background: Recent evidence suggests decreased expression of synapticrelated genes and loss of synapses in major depressive disorder (MDD), and the decreased expression of pre-synaptic-related genes is accompanied by an increased expression of the depression-associated transcription factor GATA1 transcriptional factor. Depression is also linked to cognitive decline, including in Alzheimer disease (AD), but the exact nature of the relationship is poorly understood. In this study, we explored the GATA1 expression in postmortem AD brains and examined the causal effect of GATA1 on amyloid processing in neuronal cells experimentally. Methods: Frontal cortex region (BM9) from 24 post mortem AD subjects were analyzed by qPCR for the depression-associated transcription factor GATA1 and synaptic genes. To assess a potential causal role of GATA1 on amyloid processing we examined b-amyloid level and downstream synaptic gene expression in neuronal cells expressing exogenous GATA1. Results:We found a significant elevation of GATA1 in the BM9 region of AD brains (CDR1⁄45) as compared to normal subjects (CDR1⁄40). Coincidentally, we also found decreased expression of some pre-synaptic genes (e.g. synapsin1, calmodulin2 and rab3a). Interestingly, GATA1 expresison was positive correlated with the b-amyloid plaque count. Exogenous expression of GATA1 in neuronal cells resulted in decreased expression of pre-synaptic genes as well as elevated b-amyloid level. Conclusions: Our study for the first time suggests that the depression-associated transcription factor GATA1 expression may influence synaptic plasticity and eventually cognitive function in AD brain through mechanisms involving AD-type neuropathology.