Confluence of α-synuclein, tau, and β-amyloid pathologies in dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is pathologically characterized by α-synuclein aggregates in the brain. Most patients with DLB also show cerebral Alzheimer disease-type pathology (i.e. β-amyloid plaques and hyperphosphorylated tau deposits). It is unclear whether this overlap is coincidental or driven by specific regional or cellular interactions. The aims of this study were to investigate the regional convergence of α-synuclein, tau, and β-amyloid and to identify patterns of cellular co-occurrence of tau and α-synuclein in DLB. The study group consisted of 22 patients who met clinical and neuropathologic criteria for DLB. Protein aggregates were assessed semiquantitatively in 17 brain areas. APOE and MAPT genotypes were determined. Cellular co-occurrence of tau and α-synuclein was evaluated by double immunofluorescence. We found that total β-amyloid pathology scores correlated positively with total α-synuclein pathology scores (ρ = 0.692, p = 0.001). The factors that correlated best with the amount of α-synuclein pathology were the severity of β-amyloid pathology and presence of the MAPT H1 haplotype. Tau and α-synuclein frequently colocalized in limbic areas, but no correlation between total pathology scores was observed. This study confirms and extends the role of β-amyloid deposition and the MAPT H1 haplotype as contributing factors in DLB pathogenesis and demonstrates the confluence of multiple agents in neurodegenerative diseases.
From the Neurology Department, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain (MC-C, OB, RB, JC, AL); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain (MC-C, OB, RB, MJM, JC, AL); Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (EG, SC); Parkinson Disease & Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències (ICN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain (MJM).
Martí
M
Colom-Cadena
Ellen
E
Gelpi
Sara
S
Charif
Olivia
O
Belbin
Rafael
R
Blesa
Maria J
MJ
Martí
Jordi
J
Clarimón
Alberto
A
Lleó
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D051844:alpha-Synuclein; D016875:tau Proteins