Neurodegeneration, synaptic dysfunction, and gliosis are phenotypic of Alzheimer dementia

作者：Merluzzi Andrew P^*; Carlsson Cynthia M; Johnson Sterling C; Schindler Suzanne E; Asthana Sanjay; Blennow Kaj; Zetterberg Henrik; Bendlin Barbara B

来源：Neurology, 2018, 91(5): E436-E443.

DOI：10.1212/WNL.0000000000005901

Objective
To test the hypothesis that cognitively unimpaired individuals with Alzheimer disease (AD) neuropathology differ from individuals with AD dementia on biomarkers of neurodegeneration, synaptic dysfunction, and glial activation.
Methods
In a cross-sectional study, adult participants >70 years old (n = 79, age 77.1 +/- 5.3 years) underwent comprehensive cognitive evaluation and CSF collection, which was assayed for markers of amyloid, phosphorylated tau (p-tau), neurodegeneration (neurofilament light protein [NFL] and total tau), synaptic dysfunction (neurogranin), and glial activation (chiti-nase-3-like protein 1 [YKL-40]). Participants were divided into 3 groups based on diagnosis and p-tau/beta-amyloid42 (A beta 42): those with low p-tau/A beta 42 and unimpaired cognition were classified as controls (n = 25); those with high p-tau/A beta 42 diagnosed with AD-dementia or AD-mild cognitive impairment were classified as AD-Dementia (n = 40); and those with high p-tau/A beta 42 but unimpaired cognition were classified as mismatches (n = 14). A similar, secondary analysis was performed with no age exclusion criteria (n = 411).
Results
In both the primary and secondary analyses, biomarker levels between groups were compared with the use of analysis of covariance while controlling for age and demographic variables. Despite p-tau/A beta 42 and A beta 42/A beta 40 levels comparable to those of the AD-Dementia group, mismatches had significantly lower levels of NFL and total tau. While not significantly lower than the AD-Dementia group on YKL-40 and neurogranin, mismatches were also not significantly different from controls.
Conclusions
These results provide evidence that, in the absence of significant neurodegenerative processes, individuals who harbor AD neuropathology may remain cognitively unimpaired. This finding provides insight into the biological processes phenotypic of dementia and supports monitoring multiple biomarkers in individuals positive for AD neuropathology.

• 出版日期2018-7-31