Evidence that the Kennedy and polyamine pathways are dysregulated in human brain in cases of dementia with Lewy bodies.

Evidence that the Kennedy and polyamine pathways are dysregulated in human brain in cases of dementia with Lewy bodies. Brain Res. 2020 May 22;:146897 Authors: Akyol S, Yilmaz A, Joon Oh K, Ugur Z, Aydas B, McGuinness B, Passmore P, Kehoe PG, Maddens M, Green BD, Graham SF Abstract Disruptions of brain metabolism are considered integral to the pathogenesis of dementia, but thus far little is known of how dementia with Lewy bodies (DLB) impacts the brain metabolome. DLB is less well known than other neurodegenerative diseases such as Alzheimer's and Parkinson's disease which is perhaps why it is under-investigated. This exploratory study aimed to address current knowledge gaps in DLB research and search for potentially targetable biochemical pathways for therapeutics. It also aimed to better understand metabolic similarities and differences with other dementias. Combined metabolomic analyses of 1H NMR and tandem mass spectrometry of neocortical post-mortem brain tissue (Brodmann region 7) from autopsy confirmed cases of DLB (n=15) were compared with age/gender-matched, non-cognitively impaired healthy controls (n=30). Following correction for multiple comparisons, only 2 metabolites from a total of 219 measured compounds significantly differed. Putrescine was suppressed (55.4%) in DLB and O-phosphocholine was elevated (52.5%). We identified a panel of 5 metabolites (PC aa C38:4, O-Phosphocholine, putrescine, 4-Aminobutyrate, and SM C1...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research