Plasma biomarkers as prognostic markers in Alzheimer’s disease: Influence of age at onset

Abstract

AbstractBackgroundLittle is known about the influence of age at onset (AAO) on plasma biomarkers and their use as prognostic biomarkers in Alzheimer’s disease (AD).MethodWe selected patients with AD diagnosis with available neuropsychological testing (NPS) at time of diagnosis and two years later, and plasma biomarkers at baseline.NPS battery included Free and Cued Selective Reminding Test (FCSRT), Landscape test (visual memory), Boston Naming Test, Semantic Fluency, BDAE auditory comprehension, Constructional and Ideomotor Praxis, Visual Object and Space Perception (VOSP) Incomplete Letters and Number Location subtests, Trail Making Test (TMT) A and B, Phonemic Fluency, and Digit Span Forward and Backward. NPS scores were compared by AAO: early‐onset AD (EOAD; <65 years) vs. late onset AD (LOAD; >65y).We analyzed plasma biomarkers phosphorilated‐tau181 (p‐tau181), total tau (t‐tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin C‐terminal hydrolase L1 (UCHL‐1) using the Quanterix Simoa p‐tau181 Advantage V2 and Neurology 4‐Plex A assays. Group comparisons and linear regressions adjusted by years of education (YOE) were performed in Stata/IC 16.1.ResultForty‐two participants were included, 23 LOAD and 19 EOAD. Plasma p‐tau181 and GFAP levels were higher in LOAD (Table 1). We did not find differences between LOAD and EOAD in NPS tests at baseline or +2 years (Table 2).Plasma ptau‐181 was associated with progression in MMSE globally, VOSP‐Incomplete letters globally and in EOAD. Plasma NfL were associated to Boston Naming test globally and in EOAD, Semantic fluency test globally, VOSP‐incomplete letters in EOAD, and Free and Total Learning of FCSRT in LOAD. Plasma GFAP was associated to MMSE globally and in EOAD, Free learning of FCSRT in LOAD and VOSP‐Incomplete letters and number location globally. Plasma UCHL‐1 was associated to Semantic fluency test in LOAD (Table 3). Praxis and attention and executive function tests loss were not associated to plasma biomarkers.ConclusionPlasma p‐tau18, NfL, GFAP and UCHL‐1 were associated to pogression in memory, language and visual tests. They were predominantly associated to memory loss in LOAD and language and visual function loss in EOAD. Results need to be interpreted cautiously due to small sample size.