β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, multicentrická studie, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P50 AG016574
NIA NIH HHS - United States
R37 AG011378
NIA NIH HHS - United States
R01 AG041851
NIA NIH HHS - United States
C06 RR018898
NCRR NIH HHS - United States
R01 AG040042
NIA NIH HHS - United States
U01 AG006786
NIA NIH HHS - United States
U01 NS100620
NINDS NIH HHS - United States
R01 AG011378
NIA NIH HHS - United States
R01 NS080820
NINDS NIH HHS - United States
PubMed
32989106
PubMed Central
PMC7836666
DOI
10.1212/wnl.0000000000010943
PII: WNL.0000000000010943
Knihovny.cz E-zdroje
- MeSH
- amyloidní beta-protein mozkomíšní mok metabolismus MeSH
- apolipoprotein E4 genetika MeSH
- biologické markery metabolismus MeSH
- demence s Lewyho tělísky klasifikace komplikace metabolismus patofyziologie MeSH
- fenotyp MeSH
- kognitivní dysfunkce etiologie patofyziologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- pozitronová emisní tomografie MeSH
- proteiny tau mozkomíšní mok metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- amyloid beta-protein (1-42) MeSH Prohlížeč
- amyloidní beta-protein MeSH
- apolipoprotein E4 MeSH
- biologické markery MeSH
- peptidové fragmenty MeSH
- proteiny tau MeSH
OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+. RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.
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