Biomarkers for Differential Diagnosis Between Chronic Traumatic Encephalopathy and Alzheimer Disease: A Systematic Review

Objective To assess the diagnostic utility of biomarkers that could differentiate Chronic Traumatic Encephalopathy (CTE) from Alzheimer disease (AD).

Background CTE is a neurodegenerative disease associated with multiple head trauma. The diagnosis depends on neuropathologic findings postmortem, and patients can present cognitive and behavioral changes. These symptoms can usually be mistaken for other dementias, such as AD, leading to an underestimated frequency of CTE. Therefore, specific biomarkers can be useful for comprehending disease development, diagnosis and prognosis.

Design/Methods We systematically searched the MEDLINE, Embase and Cochrane databases. We also searched the trial registries and reference lists of articles. We included studies that were relevant to the PICO question posed and analysed different biomarkers. We screened titles and abstracts and if they were pertinent, we assessed the full text and reported results narratively.

Results Twenty-two studies were identified through database searching. One study was excluded due to duplicity among the databases. Twenty-one articles were assessed for eligibility and 6 were included in the qualitative synthesis. P-Tau and T-tau proteins were indicated as biomarkers of neurodegenerative diseases such as CTE and AD, but not from other tauopathies. Exosomal tau levels are higher in CTE patients than in AD patients, and it might be useful since it is very stable, crosses the blood–brain barrier and reflects their cellular origin. Pathophysiologic differences between CTE and AD are pointed out as a way to find specific biomarkers for CTE. The biomarkers associated with neuroaxonal damage (NFL), glial response with astroglial scarring (GFAP and sTREM2), and microvascular damage with disruption of the blood–brain barrier (cerebrospinal fluid/serum albumin ratio) are promising in that way.

Conclusions Biomarkers that arise from pathophysiologic processes distinct from the 2 diseases, appear to be promising. However, further well-designed studies are needed to assess the real utility of the biomarkers in differential diagnosis between CTE and AD.