Does Alzheimer’s tau hit retinal ganglion cells early?

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In 41 donor eyes, MCI and AD retinas showed pS396-tau and oligomeric tau inside RGCs, ~50% ganglion-cell loss, and correlations with brain AD stage and cognition.

Source

Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease

Davis MR, Robinson E, Koronyo Y, et al. · Acta neuropathologica communications · 2025

doi.org/10.1186/s40478-025-01935-y Read the full paper ↗31 citationscc by

Study at a glance

Design: Case-control — Human donor retina/brain comparison of AD dementia, MCI due to AD, and cognitively normal controls
N: N=41 · AD dementia n=15, MCI due to AD n=10, CN controls n=16
Population: Human retinal superior-temporal cross-sections and matched brain donors spanning MCI due to AD, AD dementia, and CN controls
Outcome: Pathogenic tau in RGCs (pS396-tau, oligomeric tau), RGC loss/morphology, and correlations with brain AD pathology and cognition

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What they did

Quantified RGC number, morphology, and abnormal tau isoforms (pS396-tau, Oligo-tau) in superior temporal retina from MCI due to AD, AD dementia, and CN controls, and related findings to brain pathology and cognitive status.

What they found

First evidence of RGCs laden with pS396-tau and oligomeric tau in MCI and AD, with hypertrophic somas and apoptotic/GVD-necroptotic markers, ~50% RGC loss, and strong correlations between tau-laden RGCs and brain AD pathology, stage, and cognition.

The limits

What it doesn't show

Postmortem case-control data cannot prove retinal imaging will diagnose living patients; further work is needed before using tau-laden RGCs as a clinical biomarker.

Key terms

RGC: Retinal ganglion cell, the output neuron of the retina.
pS396-tau: Tau phosphorylated at serine 396, a pathogenic isoform.
Oligo-tau: Oligomeric tau species measured in RGCs here.
MCI due to AD: Mild cognitive impairment attributed to Alzheimer’s disease.
RBPMS: Marker used to identify RGCs in retinal tissue.

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CN control N was:

Common questions

Who was in the human cohort?

AD dementia n=15, MCI due to AD n=10, CN n=16.

What tau species were in RGCs?

pS396-tau and oligomeric tau.

How much RGC loss?

About 50% ganglion cell loss in MCI/AD retinas.

Clinical implication suggested?

Imaging tau-laden RGCs as a possible non-invasive AD biomarker.