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P1‐087: Microarray analysis of human neuroblastoma cells exposed to beta‐amyloid, aluminum, and the beta‐amyloid‐aluminum complex
Author(s) -
Gatta Valentina,
Drago Denise,
Sensi Stefano L.,
Zatta Paolo
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.2010.05.635
Subject(s) - microarray , microarray analysis techniques , alexa fluor , microbiology and biotechnology , amyloid beta , gene knockdown , gene , gene expression , dna microarray , amyloid (mycology) , chemistry , rna , biology , biochemistry , peptide , inorganic chemistry , physics , quantum mechanics , fluorescence
with amnestic mild cognitive impairment (MCI) were examined by gender and genotype. Results: In early AD, male gender and butyrylcholinesterase (BuChE)-K carrier status, if accompanied by apolipoprotein E (APOE) e4 carrier status, results in prominent damage to grey and white matter in the medial temporal region and cognitive decline due to direct toxic effects of aggregated Ab on cholinergic synapses, neurons, myelin and oligodendrocytes. Symptoms can be attenuated by increasing synaptic acetylcholine (ACh) in damaged, but still functional, cholinergic synapses. Conversely, chronic glial overactivation, that is more likely in females and due, at least in part, to extracellular ACh deficits, can also drive neurodegenerative processes. In females with wild-type BuChE, glial overactivation may be the main driver from MCI to AD. Females are more likely than males to have accelerated age-related myelin breakdown, more widespread white matter loss, loss of neural network connectivity, whole brain atrophy and functional decline. Damage to neural network connectivity can be attenuated by increasing extracellular ACh and this is disease-modifying. Conclusions: Identification of phenotypes is important to appropriately target dementia therapy and interpret biomarker data. Preservation of the functional integrity of the neural network may be an important component of strengthening cognitive reserve and significantly delaying the onset and progression of dementia, particularly in females. Prospective confirmation of these hypotheses is required.