Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment

Abstract

ABSTRACT.Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies.Objective:To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden.Methods:Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aβ1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aβ1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test.Results:T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aβ1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aβ1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores.Conclusion:We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.

Pharmacological Modulators of Tau Aggregation and Spreading

“…Such release is thought not to be connected with the propagation of tau, indicating that secretion might normally be a regulated process that becomes disrupted in diseased brains [ 25 , 134 ]. Increased levels of tau were also detected in the cerebrospinal fluid (CSF) and in the brain interstitial fluid (ISF) of wild-type and transgenic mice as well as in healthy and AD individuals [ 135 , 136 , 137 , 138 , 139 ]. In a recent study, the tau spreading hypothesis was investigated using positron emission tomography (PET) in human brains.…”

Biomarcadores no Líquido Cefalorraquidiano no Desenvolvimento da Doença de Alzheimer: Uma Revisão Sistemática

“…Dessa maneira, esses dados podem ser úteis como auxílio complementar ou, até mesmo, para quantificar o grau de degeneração ativa no momento da coleta. Magalhães et al (2015) e Radanovic et al (2017) avaliaram os marcadores em pacientes com DA, com CCL e com outras demências comparando com grupos controle. Eles encontraram valores elevados para T-tau e P-tau, e reduzidos para Aβ no grupo DA, quando comparado aos grupos CCL e de outras demências.…”

“…Além disso, eles sugerem uma complementação do diagnóstico final, sempre que possível, por meio de exames de imagem, como a ressonância magnética (RM) e a tomografia computadorizada por emissão de pósitrons (PET). Os achados de Correa et al (2011) são consistentes com os outros estudos anteriores (Magalhães et al, 2015;Radanovic et al, 2017), pois mostram níveis aumentados de P-tau e níveis diminuídos de Aβ no LCR de pacientes com DA.…”