Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

• Published in: Alzheimer's & dementia Vol. 15; no. 5; pp. 644 - 654
• Main Authors: Bos, Isabelle, Vos, Stephanie, Verhey, Frans, Scheltens, Philip, Teunissen, Charlotte, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni, Blin, Olivier, Richardson, Jill C., Bordet, Régis, Tsolaki, Magda, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Lleó, Alberto, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Vandenberghe, Rik, Westwood, Sarah, Dobricic, Valerija, Barkhof, Frederik, Legido-Quigley, Cristina, Bertram, Lars, Lovestone, Simon, Streffer, Johannes, Andreasson, Ulf, Blennow, Kaj, Zetterberg, Henrik, Visser, Pieter Jelle
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2019; Alzheimer's Association / Wiley
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides; Amyloid-beta; Amyloid-β; APOE; Apolipoprotein E4 - genetics; association; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cognition; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - physiopathology; Cognitive science; degeneration; Female; Geriatrik; guidelines; Humans; Klinisk laboratoriemedicin; Klinisk medicin; Medicin och hälsovetenskap; mild cognitive impairment; Neurofilament light; Neurofilament Proteins - cerebrospinal fluid; Neurogranin; Neurogranin - cerebrospinal fluid; Neurologi; Neuroscience; Neurosciences; Neurovetenskaper; pathology; protein; tau; tau Proteins - cerebrospinal fluid; YKL-40; Neurogranin; Neurofilament light; Cognition; Amyloid-β; Cerebrospinal fluid; APOE; YKL-40; Alzheimer's disease
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1016/j.jalz.2019.01.004

We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).
We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ− vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.
Ng and T-tau distinguished between Aβ+ from Aβ− individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.
Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.