Findings from a recent exploratory study published in IOS Press suggest a significant tie between biomarkers within the eye’s vitreous humor as well as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE),
Let’s start with some background.
AD and CTE are typically diagnosed from symptoms, clinical exam findings, and cognitive testing after a post-mortem brain examination.
Patients with eye disease are known to have an increased risk for developing a neurodegenerative disease like AD; similarly, these diseases have been tied to ophthalmic conditions like glaucoma, cataract, and age-related macular degeneration (AMD).
However, there has yet to be an established link identified between ocular fluid biomarker levels with a diagnosis of such diseases like AD.
Now this research.
In this exploratory, retrospective study, researchers examined 41 eyes and brain tissue (postmortem) of patients (median age of 72) with a diagnosis of AD (n = 7), CTE (N = 15), AD + CTE (N = 10), and no neuropathology (n =9).
And the participants?
All participants were selected from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) brain bank at Boston University; each was selected at less than 72 hours postmortem.
Inclusion criteria consisted of a history of repetitive head injury (RHI) and moderate to severe traumatic brain injury (TBI).
What was measured?
An immunoassay analysis quantitatively measured protein biomarkers, which included:
- amyloid-β (Aβ40,42)
- total tau (tTau)
- phosphorylated tau (pTau181,231)
- neurofilament light chain (NfL)
- eotaxin-1
Non-parametric tests compared vitreous biomarker levels between each group and Spearman’s rank correlation tests connected biomarker levels in vitreous and cortical tissue.
To note, the significance level was set at α= 0.10.
Findings?
Out of all proteins, tTau levels significantly increased in the AD and CTE groups (p = 0.08; both) compared to the control group as well as for the AD group vs AD + CTE group and the CTE group vs AD + CTE group (p = 0.049; both).
What about the other protein levels?
Vitreous NfL levels were noted as significantly increased for low CTE compared to no CTE (p = 0.096) as well as in low CTE compared to high CTE stage (p = 0.03).
Significant correlations were also observed in the vitreous and cortical tissue levels for pTau 231 (p = 0.02, r = 0.38) and tTau (p = 0.04, r = –0.34).
Limitations?
The investigators identified the small sample size of the study (due to the reliance on donations of post-mortem brain and ocular tissue) as well as the young average age of participants, which could influence tTau levels (known to increase with aging).
See here for other limitations.
Significance?
According to the study authors, this is the first research that has investigated (and confirmed) a link between vitreous fluid biomarkers and a post-mortem brain tissue pathological examination of AD as well as CTE.
It also supports the authors’ prior research on biomarkers in vitreous fluids that identified a link to cognitive function in living patients with both normal cognition and mild cognitive impairment.
They suggest that these findings may provide a basis for future investigation of biomarkers and other ocular fluids in diagnosing and managing AD and CTE.