A study shows Alzheimer’s disease biomarkers in the vitreous

Alzheimer’s disease leads to severe cognitive dysfunction and eventual death; by 2050 it is expected to affect more than 115 million people worldwide. From time of diagnosis until death the average survival time is just under 5 years. Even with advances in medicine, a clinical diagnosis is only confirmed post-mortem, said Manju L. Subramanian, MD, Boston Medical Center.

Most patients will be asymptomatic until later stage of disease, which can be too late for current therapies to have any meaningful effect, she said.

“There is a need for sensitive and specific tests for the early diagnosis of Alzheimer’s,” she said.

The eye may hold the key.

There may be a lot of overlap between what happens in the eye and what happens in the brain.

“Other studies have found protein biomarkers in the eye, but those findings were reported years ago and their findings were not correlated to cognitive status. We wanted to capture the patient population with eye disease but who did not have a known diagnosis of Alzheimer’s Disease or other forms of dementia. Levels of amyloid beta (Aß) plaques are increased in the brain but decreased in the cerebrospinal fluid of those with Alzheimer’s. Levels of neurofibrillary tangles (Tau) are increased in both the brain and cerebrospinal fluid of those with Alzheimer’s.

Study details
Dr. Subramanian initiated a cross-sectional study to determine if known biomarkers for Alzheimer’s disease in the vitreous humor correlated with cognitive function. She enrolled 80 patients already scheduled for vitrectomy who then underwent a mini-mental status examination (MMSE) to assess cognitive function. A diagnosis of dementia or Alzheimer’s was not exclusionary.

Of those 80 subjects, nine (5 males, 4 females) exhibited mild (n=8) to severe (n=1) levels of cognitive impairment based on MMSE scores.

Vitreous samples were taken (0.5-2.0 mms undiluted), and the samples were analyzed by ELISA. Higher vitreous levels of Aß40 (p=0.015), Aß 42 (p=0.0066), and tTau (p=0.0085) were significantly associated with better MMSE scores, while lower vitreous levels were associated with lower MMSE scores.

“Our findings are consistent with the abnormally low levels of Aß observed in the cerebrospinal fluid in patients with Alzheimer’s compared with cognitively normal subjects,” she said. “The study confirms that Alzheimer’s disease biomarkers exist in the vitreous, and their correlation to cognition suggest that protein biomarkers in the vitreous has a potential role as an early diagnostic tool.”

Next steps
For Dr. Subramanian, the next step in the research is how to translate the data into something that is clinically useful.

“We obviously can’t screen everyone’s vitreous,” she said.

There may be a role for optical coherence tomography (OCT) as well, and several studies have shown significant findings in patients with cognitive impairment.  But other eye diseases like glaucoma affect the nerve fiber layer in a similar manner as Alzheimer’s, which may limit the effectiveness of OCT, she said.

“Patients with eye disease are probably an at-risk population for Alzheimer’s disease. We see patients with eye complications from diabetes, and Type 2 diabetes is a well-known risk factor for Alzheimer’s,” Dr. Subramanian said. “So whatever we’re able to find in patients with eye disease may be generalizable to the rest of the population as well.”

Disclosures:

Dr. Subramanian presented her study results to the American Society of Retina Specialists meeting in Vancouver. She has no financial disclosures to report.