Cerebrospinal fluid biomarkers and cognitive trajectories in patients with Alzheimer’s disease and a history of traumatic brain injury

• Published in: Neurobiology of aging 2024-09, Vol.141, p.121-128
• Main Authors: van Amerongen, Suzan, Das, Shreyasee, Kamps, Suzie, Goossens, Julie, Bongers, Bram, Pijnenburg, Yolande A.L., Vanmechelen, Eugeen, Vijverberg, Everard G.B., Teunissen, Charlotte E., Verberk, Inge M.W.
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Cerebrospinal fluid; Cognitive decline; Synaptic biomarkers; Traumatic brain injury
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2024.06.001

Traumatic brain injury (TBI) and Alzheimer’s disease (AD) have overlapping mechanisms but it remains unknown if pathophysiological characteristics and cognitive trajectories in AD patients are influenced by TBI history. Here, we studied AD patients (stage MCI or dementia) with TBI history (ADTBI+, n=110), or without (ADTBI-, n=110) and compared baseline CSF concentrations of amyloid beta 1–42 (Aβ42), phosphorylated tau181 (pTau181), total tau, neurofilament light chain (NfL), synaptosomal associated protein-25kDa (SNAP25), neurogranin (Ng), neuronal pentraxin-2 (NPTX2) and glutamate receptor-4 (GluR4), as well as differences in cognitive trajectories using linear mixed models. Explorative, analyses were repeated within stratified TBI groups by TBI characteristics (timing, severity, number). We found no differences in baseline CSF biomarker concentrations nor in cognitive trajectories between ADTBI+ and ADTBI- patients. TBI >5 years ago was associated with higher NPTX2 and a tendency for higher SNAP25 concentrations compared to TBI ≤ 5 years ago, suggesting that TBI may be associated with long-term synaptic dysfunction only when occurring before onset or in a pre-clinical disease stage of AD. •History of TBI is not associated with distinct cognitive trajectories in AD.•History of remote TBI in AD may be linked to alterations in CSF synaptic biomarkers.•Independent of TBI, CSF NfL and NPTX2 are predictors for cognitive decline in AD.