Affiliations: [a]
Laboratory of Neuroscience, Departamento e Instituto de Psiquiatria HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil
| [b]
Instituto Nacional de Biomarcadores em Neuropsiquiatria (InBion), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Sao Paulo, Brazil. | [c]
Universidade Estadual de Goias, Goias, Brazil
Correspondence:
[*]
Correspondence to: Prof. Dr. Orestes V. Forlenza, Instituto de Psiquiatria do Hospital das Clínicas da FMUSP, Dr. Ovídio Pires de Campos 785, 1st floor, suite 1S07, 05403-010, Sao Paulo, SP, Brazil. Tel.: +55 11 2661 7539; E-mail: forlenza@usp.br.; https://orcid.org/0000-0002-6962-5899
Abstract: Background:Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer’s disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice. Objective:To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. Methods:204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (n = 60, 29.4%); MCI (n = 84, 41.2%); or normal cognition (NC, n = 60, 29.4%). CSF concentrations of Aβ42, T-tau, and 181Thr-P-tau were determined, and Aβ42/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD. Results:The majority (73.7%) of patients in the AD group had the Aβ42/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as N + . In the AD group, 66.7%of the cases were classified as A+, 78.3%as T+, and 80%as N+. Conclusion:Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.
