Abnormal tau in amyloid PET negative individuals

Area of Science:

• Neurodegenerative diseases
• Biomarker research
• Alzheimer's disease diagnostics

Background:

• Alzheimer's disease (AD) is typically characterized by both amyloid-beta (Aβ) plaques and tau tangles.
• Investigating individuals with tau pathology but without Aβ (A-T+) is crucial for understanding AD heterogeneity.
• The Alzheimer's Disease Neuroimaging Initiative (ADNI) provides valuable data for such investigations.

Purpose of the Study:

• To characterize individuals with tauopathy and no Aβ (A-T+) compared to those with and without both AD biomarkers (A+T+ and A-T-).
• To explore the relationship between A-T+ status, demographics, neuroimaging, and cognitive function.
• To determine if the A-T+ group represents a distinct pathological entity or a spectrum of neurodegenerative conditions.

Main Methods:

• Analysis of 561 participants from the ADNI cohort with Aβ and tau Positron Emission Tomography (PET).
• Comparison of demographic, biomarker (amyloid, tau), neuroimaging (hippocampal volumes), and cognitive data across A-T-, A-T+, and A+T+ groups.
• Assessment of tau deposition patterns and apolipoprotein E ɛ4 (APOE4) prevalence in the A-T+ group.

Main Results:

• The A-T+ group (n=63) exhibited intermediate severity of tau deposition, hippocampal atrophy, and cognitive impairment compared to A-T- (n=316) and A+T+ (n=182) groups (p < 0.001).
• A-T+ individuals had low APOE4 prevalence (17%) and no evidence of elevated Aβ within the negative range.
• Tau PET patterns in A-T+ individuals were heterogeneous: 29% showed medial temporal lobe tau (primary age-related tauopathy), and 32% showed AD-consistent tau patterns.

Conclusions:

• The A-T+ group shares AD-like features such as cognitive impairment and neurodegeneration, but is pathologically heterogeneous.
• This heterogeneity suggests that the A-T+ classification may encompass more than one distinct neurodegenerative disorder.
• Further research is needed to differentiate the underlying pathologies within the heterogeneous A-T+ group.