Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.

BACKGROUND: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) µm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.

Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals.

In an immune response, CD4(+) T cells expand into effector T cells and then contract to survive as long-lived memory cells. To identify age-associated defects in memory cell formation, we profiled activated CD4(+) T cells and found an increased induction of the ATPase CD39 with age. CD39(+) CD4(+) T cells resembled effector T cells with signs of metabolic stress and high susceptibility to undergo apoptosis. Pharmacological inhibition of ATPase activity dampened effector cell differentiation and improved survival, suggesting that CD39 activity influences T cell fate. Individuals carrying a low-expressing CD39 variant responded better to vaccination with an increase in vaccine-specific memory T cells. Increased inducibility of CD39 after activation may contribute to the impaired vaccine response with age.