TY - JOUR
T1 - CSF biomarkers in Olmsted County
T2 - Evidence of 2 subclasses and associations with demographics
AU - Van Harten, Argonde C.
AU - Wiste, Heather J.
AU - Weigand, Stephen D.
AU - Mielke, Michelle M.
AU - Kremers, Walter K.
AU - Eichenlaub, Udo
AU - Batrla-Utermann, Richard
AU - Dyer, Roy B.
AU - Algeciras-Schimnich, Alicia
AU - Knopman, David S.
AU - Jack, Clifford R.
AU - Petersen, Ronald C.
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2020/7/21
Y1 - 2020/7/21
N2 - ObjectiveWe studied interrelationships between CSF biomarkers and associations with APOE ϵ4 genotype, demographic variables, vascular variables, and clinical diagnosis in Olmsted County, Minnesota.MethodsWe included 774 Mayo Clinic Study of Aging participants (693 cognitively unimpaired [CU]; 71 with mild cognitive impairment [MCI]). CSF β-amyloid 42 (Aβ42), total tau (t-tau), and hyperphosphorylated tau (p-tau) were analyzed using Aβ42 CSF, t-tau CSF, and p-tau (181P) CSF electrochemiluminescence immunoassays. Bivariate mixture models were used to evaluate latent classes. We used linear regression models to evaluate independent associations of APOE ϵ4, demographic factors, cardiovascular risk, and diagnosis with CSF biomarker levels. Results were weighted back to the Olmsted County population.ResultsInterrelationships between CSF Aβ42 and p-tau/t-tau were consistent with 2 latent classes in the general population. In subgroup 1 (n = 547 [71%]), we found a strong positive correlation between Aβ42 and p-tau (ρ = 0.81), while the correlation was much smaller in group 2 (ρ = 0.26, n = 227 [29%]). Group 2 was associated with older age, APOE ϵ4 genotype, a diagnosis of MCI, and elevated amyloid PET. Overall, APOE ϵ4 genotype and MCI were associated with Aβ42, while age was associated with p-tau/t-tau. There were no associations with sex, education, or vascular risk.ConclusionWe hypothesize the population without dementia can be subdivided into participants with and without biological Alzheimer disease (AD) based on the combination of CSF Aβ42 and p-tau/t-tau (represented also by the p-tau/t-tau/Aβ42 ratio). In those without biological AD, common factors such as CSF dynamics may cause a positive correlation between CSF Aβ42 and p-tau/t-tau, while AD leads to dissociation of these proteins.
AB - ObjectiveWe studied interrelationships between CSF biomarkers and associations with APOE ϵ4 genotype, demographic variables, vascular variables, and clinical diagnosis in Olmsted County, Minnesota.MethodsWe included 774 Mayo Clinic Study of Aging participants (693 cognitively unimpaired [CU]; 71 with mild cognitive impairment [MCI]). CSF β-amyloid 42 (Aβ42), total tau (t-tau), and hyperphosphorylated tau (p-tau) were analyzed using Aβ42 CSF, t-tau CSF, and p-tau (181P) CSF electrochemiluminescence immunoassays. Bivariate mixture models were used to evaluate latent classes. We used linear regression models to evaluate independent associations of APOE ϵ4, demographic factors, cardiovascular risk, and diagnosis with CSF biomarker levels. Results were weighted back to the Olmsted County population.ResultsInterrelationships between CSF Aβ42 and p-tau/t-tau were consistent with 2 latent classes in the general population. In subgroup 1 (n = 547 [71%]), we found a strong positive correlation between Aβ42 and p-tau (ρ = 0.81), while the correlation was much smaller in group 2 (ρ = 0.26, n = 227 [29%]). Group 2 was associated with older age, APOE ϵ4 genotype, a diagnosis of MCI, and elevated amyloid PET. Overall, APOE ϵ4 genotype and MCI were associated with Aβ42, while age was associated with p-tau/t-tau. There were no associations with sex, education, or vascular risk.ConclusionWe hypothesize the population without dementia can be subdivided into participants with and without biological Alzheimer disease (AD) based on the combination of CSF Aβ42 and p-tau/t-tau (represented also by the p-tau/t-tau/Aβ42 ratio). In those without biological AD, common factors such as CSF dynamics may cause a positive correlation between CSF Aβ42 and p-tau/t-tau, while AD leads to dissociation of these proteins.
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U2 - 10.1212/WNL.0000000000009874
DO - 10.1212/WNL.0000000000009874
M3 - Article
C2 - 32591471
AN - SCOPUS:85088494062
SN - 0028-3878
VL - 95
SP - E256-E267
JO - Neurology
JF - Neurology
IS - 3
ER -