# The relationships between ethnoracial identity, Aβ positivity, APOEε4, and medial temporal lobe tau PET

**Authors:** Koral V. Wheeler, Victoria R. Tennant, Noelle N. Lee, Maxwell W. Hand, Suchita Ganesan, Patrick Walsh, Meral Tubi, Jamie A. Terner, Brandon Hall, Marylan Davison, Arthur W. Toga, Sid O'Bryant, Alexandra L. Clark, Kristine Yaffe, Meredith N. Braskie, Meredith Braskie, Meredith Braskie, Kevin King, James R Hall, Melissa Petersen, Raymond Palmer, Robert Barber, Yonggang Shi, Fan Zhang, Rajesh Nandy, Roderick McColl, David Mason, Bradley Christian, Nicole Phillips, Stephanie Large, Joe Lee, Badri Vardarajan, Monica Rivera Mindt, Amrita Cheema, Lisa Barnes, Mark Mapstone, Annie Cohen, Amy Kind, Ozioma Okonkwo, Raul Vintimilla, Zhengyang Zhou, Michael Donohue, Rema Raman, Matthew Borzage, Michelle Mielke, Beau Ances, Ganesh Babulal, Jorge Llibre-Guerra, Carl Hill, Rocky Vig

PMC · DOI: 10.1002/alz.71226 · Alzheimer's & Dementia · 2026-03-04

## TL;DR

The study finds that Black and Hispanic participants have higher tau levels in brain regions compared to non-Hispanic Whites, but these differences may be partly due to imaging artifacts.

## Contribution

The paper reveals ethnoracial differences in tau PET signals and how off-target binding affects these findings.

## Key findings

- Black and Hispanic participants had higher medial temporal lobe tau than non-Hispanic Whites.
- Lateral temporal tau was similar across groups after adjusting for meningeal binding.
- Choroid plexus off-target binding partially explained MTL tau differences.

## Abstract

Clarifying relationships between amyloid, tau, and cognition is crucial to understanding dementia risk, but has been mainly performed in non‐Hispanic White (NHW) participants. It is unknown whether findings are generalizable to other ethnoracial groups.

We evaluated relationships between amyloid‐β (Aβ) positivity, apolipoprotein E allele (APOE) ε4, tau‐positron emission tomography (PET) 18F‐PI‐2620, and cognitive performance in 1181 cognitively unimpaired (451 NHW, 353 Hispanic, and 377 Black) and 383 mild cognitively impaired (85 NHW, 129 Hispanic, and 169 Black) participants from the Health and Aging Brain Study‐Health Disparities.

Black (β = 0.28, p < 0.001) and Hispanic (β = 0.34, p < 0.001) participants had higher medial temporal lobe (MTL) tau than NHW participants; however, findings were attenuated when accounting for choroid plexus off‐target binding. Hispanic participants showed higher tau in lateral temporal regions compared to NHW and Black participants; however, reducing meningeal off‐target binding through erosion demonstrated similar lateral temporal tau across groups.

Factors other than amyloid and tau may impact cognition in Black participants. PI2620 off‐target ethnoracial differences should be investigated.

Hispanic and Black participants showed higher medial temporal lobe (MTL) tau levels than non‐Hispanic White (NHW) participants.The relationship between amyloid‐β (Aβ), MTL tau, and cognition differed in the Black cohort.Choroid plexus off‐target binding partially contributed to MTL tau signal.Lateral temporal tau was the same across groups upon removing meningeal binding.

Hispanic and Black participants showed higher medial temporal lobe (MTL) tau levels than non‐Hispanic White (NHW) participants.

The relationship between amyloid‐β (Aβ), MTL tau, and cognition differed in the Black cohort.

Choroid plexus off‐target binding partially contributed to MTL tau signal.

Lateral temporal tau was the same across groups upon removing meningeal binding.

## Linked entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348]
- **Proteins:** MAPT (microtubule associated protein tau)
- **Diseases:** dementia (MONDO:0001627)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** hypertension (MESH:D006973), cardiovascular disease (MESH:D002318), heart attack (MESH:D009203), atrial fibrillation (MESH:D001281), cerebrovascular pathologies (MESH:D002561), type 2 diabetes (MESH:D003924), infarcts (MESH:D007238), heart failure (MESH:D006333), amyloid (MESH:C000718787), ADRD (MESH:D003704), CU (MESH:D003072), RESEARCH (MESH:D014947), dyslipidemia (MESH:D050171), MCI (MESH:D060825), AD (MESH:D000544), MTL (MESH:D004833), HD (MESH:D006816), diabetes (MESH:D003920), cerebral amyloid angiopathy (MESH:D016657), cardiomyopathy (MESH:D009202)
- **Chemicals:** 18F-flortaucipir (MESH:C000591008), florbetaben (MESH:C527756), florbetapir (MESH:C545186), PI (MESH:D010716), 18F-PI-2620 (MESH:C000710692), PI-2620 (MESH:C000722249), 18F (MESH:C000615276)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960054/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960054/full.md

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Source: https://tomesphere.com/paper/PMC12960054