HAI Book 2025 - Flipbook - Page 319
Ioannou, Konstantinos
65
Low tau in Aβ-positive cognitively impaired individuals: Alzheimer9s
disease or something more?
Konstantinos Ioannou1, Khadidzha Abdullaieva1, Richard J. Perrin2, Marina Bluma1,
Konstantinos Poulakis1, Antoine Leuzy3,4, Dorota Religa1,5, Elena Rodriguez-Vieitez1,
Konstantinos Chiotis1,5,6
1
Karolinska Institutet, Stockholm, SE
Washington University, Saint Louis, MO, US
3
University of Gothenburg, Gothenburg, SE
4
Sahlgrenska Academy, Region Västra Götaland, SE
5
Karolinska University Hospital, Stockholm, SE
6
University of California, San Francisco, CA, US
2
Aims: This study leverages biomarker and autopsy data with the aim to evaluate the impact of mixed pathologies
on interpreting cognitive impairment within the AT biomarker system.
Methods: Individuals with at least one instance of antemortem CSF AD biomarkers measurement (Roche, Elecsys
®) and a full postmortem assessment were identified from the ADNI database. Previously validated cut-offs were
used to define A+ (A´42f981 pg/mL) and T+ (p-tau181g24.3 pg/mL). A´ PET burden was quantified in-house using
the Centiloid pipeline. AT groups were compared with respect to cognitive performance, CSF ³-synuclein
positivity (Amprion, SYNTap ®), A´ PET burden, clinical comorbidities, and neuropathological evidence of
proteinopathies associated with cognitive impairment or vascular brain injury (VBI). Mixed AD was defined as the
copresence of Alzheimer9s disease neuropathological change (ADNC) and at least another non-AD proteinopathy
at autopsy.
Results: We identified and grouped 77 individuals by AT status (median [IQR] interval from CSF sampling to
death=3.13 [1.45, 5.69] years). Both A+T- and A+T+ groups were more severely cognitively impaired than the A-Tgroup at CSF sampling (Table 1). The A+T- and A+T+ groups had similar demographics, frequency of CSF ³synuclein positivity, A´ PET burden and frequency of clinical comorbidities. The groups showed differences in
APOE4 frequency. The A+T+ group showed a higher frequency of ADNC (100% vs 78%, p-value=0.008) than the
A+T- group. When ADNC was present, the A+T- group exhibited a higher frequency of mixed AD (79% vs 28%, pvalue=0.002) than the A+T+ group, even when taking VBI into consideration (Figure 1).
Conclusions: Cognitive impairment associated with A´ positivity and low tau (A+T-) is linked to mixed AD. These
cases deviate from the expected disease path, as proposed by the most recent criteria (Jack CR Jr, et al.
Alzheimers Dement. 2024) (Figure 2), and highlight the need for specific biomarkers for non-AD proteinopathies.
HAI2025 - 319
