title: Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy bodies.
abstract: Functional neuroimaging studies have consistently reported abnormalities in the visual cortex in patients with dementia with Lewy bodies (DLB), but their neuropathologic substrates are poorly understood. We analyzed synaptic proteins and choline acetyltransferase (ChAT) in the primary (BA17) and association (BAs18/19) visual cortex in DLB and similar aged control and Alzheimer disease (AD) subjects. We found lower levels of synaptophysin, syntaxin, SNAP-25, and γ-synuclein in DLB subjects versus both aged control (68%-78% and 27%-72% for BA17 and BAs18/19, respectively) and AD cases (54%-67% and 10%-56% for BA17 and BAs18/19, respectively). The loss in ChAT activity in DLB cases was also greater in BA17 (72% and 87% vs AD and control values, respectively) than in BAs18/19 (52% and 65% vs AD and control groups, respectively). The observed synaptic and ChAT changes in the visual cortices were not associated with tau or β-amyloid pathology in the occipital or the frontal, temporal, and parietal neocortex. However, the neocortical densities of LBs, particular those in BA17 and BAs18/19, correlated with lower synaptic and ChAT levels in these brain areas. These findings draw attention to molecular changes within the primary visual cortex in DLB and correlate with the neuroimaging findings within the occipital lobe in patients with this disorder.
authors.affiliation: Institute for Ageing and Health, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK. Elizabeta.Mukaetova-Ladinska@ncl.ac.uk
authors.forename: Elizabeta B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
authors.forename: Alina
authors.initials: A
authors.lastname: Andras
authors.forename: Joan
authors.initials: J
authors.lastname: Milne
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdel-All
authors.forename: Iwo
authors.initials: I
authors.lastname: Borr
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jaros
authors.forename: Robert H
authors.initials: RH
authors.lastname: Perry
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.forename: Andrea
authors.initials: A
authors.lastname: Cleghorn
authors.forename: Jeanette
authors.initials: J
authors.lastname: Doherty
authors.forename: Gary
authors.initials: G
authors.lastname: McIntosh
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Perry
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011446:Prospective Studies; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D014793:Visual Cortex / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051845:gamma-Synuclein / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; C494208:SNAP25 protein, human; C569014:SYP protein, human; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D051845:gamma-Synuclein; D002795:Choline O-Acetyltransferase