4,068 posters, 219 videos, 101 topics, 69 sessions, 14,365 authors, 6,128 institutions

Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

6776

Network-specific Patterns Of Functional Connectivity And Amyloid-ί PET Align With Tau PET In Atypical Alzheimer Disease Subtypes

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Network-specific patterns of functional connectivity and amyloid-β align with and precede tau in atypical Alzheimer disease subtypes

Peter R Millar (pmillar@wustl.edu), Stephanie Doering, Babatunde Adeyemo, Saurabh Jindal, Nicole S McKay, Jeremy F Strain, Julie K Wisch, Gordon Z An, Pete Canfield, Shaney Flores, Nicholas V Metcalf, June Roman, Carlos Cruchaga, Jason J Hassenstab, David M Holtzman, John C Morris, Brian A Gordon, Beau M Ances, Tammie LS Benzinger

Washington University in St. Louis School of Medicine

Introduction

•Spatiotemporal patterns of tau differ between distinct AD presentations^{1, 2}

•Tau accumulation may be driven by:

oTrans-neuronal spread through network connections^{2, 3}

oAmyloid-β (Aβ) deposition⁴

•Current project aims:

oReplicate tau PET subtypes in an independent cohort (Knight ADRC)

oTest subtype differences in network connectivity (RSFC) and Aβ PET

oEvaluate timing of network differences

Methods

•Defined subtypes with tau PET

o919 ¹⁸F-Flortaucipir scans from 709 participants

oStandardized SUVRs with GMM

oApplied Subtype & Stage Inference model (SuStaIn)⁵ to 5 lobe Z scores

•Tested group differences in RSFC MRI

oRetrospective scans up to 14 years before tau PET (mostly 0 to 6 years)

oGSR & censored frames > 0.2 mm FD

oSeed-based analyses with subtype-specific early tau regions as seeds

•Tested group differences in Aβ PET

oRetrospective scans up to 14 years before tau PET (mostly 0 to 6 years)

o¹¹C-PiB or ¹⁸F-Florbetapir harmonized to regional Centiloid

Results

Table. Demographic characteristics of tau PET subtypes.

Fig 1. Tau PET subtype and stage spatiotemporal patterns.

Fig 2. Elevated Aβ PET in tau regions (Fig 1) detectable when Aβ+.

Fig 3. RSFC hyperconnectivity between tau regions (Fig 1) detectable before Aβ+ or cognitive impairment.

Conclusions

•Replicated three tau subtypes with distinct clinical, genetic, and cognitive features

oS1 Limbic resembles typical AD: Most common, Braak-like tau patterns, high APOE ε4+

oS2 Posterior resembles posterior cortical atrophy (PCA): Visuospatial deficits, low ε4+

oS3 MTL-Sparing resembles early-onset AD (EOAD): Youngest age, low ε4+, most severe impairment in multiple cognitive domains

•Novel subtype differences in Aβ and RSFC hyperconnectivity align with patterns of tau

•Hyperconnectivity between tau regions may reflect network vulnerabilities that precede Aβ

•Significance: Temporal sequence of network abnormality can inform models of AD pathogenesis, clinico-pathological heterogeneity, and precision medicine tools

References

1. Graff-Radford et al. (2021) Lancet Neurol. 10.1016/S1474-4422(20)30440-3

2. Vogel et al. (2021) Nat. Med. 10.1038/s41591-021-01309-6

3. Franzmeier et al. (2020) Nat. Comms. 10.1038/s41467-019-14159-1

4. Zheng et al. (2023) Ann. Neurol. 10.1002/ana.26818

5. Young et al. (2018) Nat. Comms. 10.1038/s41467-018-05892-0

Funding

NIH K01-AG090753, P01-AG026276, P01-AG03991, P30-AG066444

Alzheimer's Association AARF-22-972678

BrightFocus Foundation A2022014F

Research Education Component (REC)

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Alzheimer's Association International Conference 2026

Network-specific Patterns Of Functional Connectivity And Amyloid-ί PET Align With Tau PET In Atypical Alzheimer Disease Subtypes

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