eprintid: 10064638 rev_number: 16 eprint_status: archive userid: 608 dir: disk0/10/06/46/38 datestamp: 2019-01-03 16:48:20 lastmod: 2021-10-23 22:49:17 status_changed: 2019-01-03 16:48:20 type: article metadata_visibility: show creators_name: Merluzzi, AP creators_name: Carlsson, CM creators_name: Johnson, SC creators_name: Schindler, SE creators_name: Asthana, S creators_name: Blennow, K creators_name: Zetterberg, H creators_name: Bendlin, BB title: Neurodegeneration, synaptic dysfunction, and gliosis are phenotypic of Alzheimer dementia ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 abstract: 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 (chitinase-3–like protein 1 [YKL-40]). Participants were divided into 3 groups based on diagnosis and p-tau/β-amyloid42 (Aβ42): those with low p-tau/Aβ42 and unimpaired cognition were classified as controls (n = 25); those with high p-tau/Aβ42 diagnosed with AD-dementia or AD–mild cognitive impairment were classified as AD-Dementia (n = 40); and those with high p-tau/Aβ42 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/Aβ42 and Aβ42/Aβ40 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. date: 2018-07-31 date_type: published publisher: LIPPINCOTT WILLIAMS & WILKINS official_url: http://doi.org/10.1212/WNL.0000000000005901 language: eng verified: verified_manual elements_id: 1567594 doi: 10.1212/WNL.0000000000005901 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Zetterberg, Henrik actors_name: Harriot, Anne-Marie actors_id: HZETT94 actors_id: AHARA72 actors_role: owner actors_role: impersonator full_text_status: restricted publication: Neurology volume: 91 number: 5 pagerange: E436-E443 pages: 8 issn: 1526-632X citation: Merluzzi, AP; Carlsson, CM; Johnson, SC; Schindler, SE; Asthana, S; Blennow, K; Zetterberg, H; Merluzzi, AP; Carlsson, CM; Johnson, SC; Schindler, SE; Asthana, S; Blennow, K; Zetterberg, H; Bendlin, BB; - view fewer <#> (2018) Neurodegeneration, synaptic dysfunction, and gliosis are phenotypic of Alzheimer dementia. Neurology , 91 (5) E436-E443. 10.1212/WNL.0000000000005901 <https://doi.org/10.1212/WNL.0000000000005901>. document_url: https://discovery.ucl.ac.uk/id/eprint/10064638/1/Merluzzi.docx