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Ossenkoppele, Coomans and colleagues analyzed the tau PET data of 12,048 individuals from 42 cohorts worldwide. They found that age, amyloid-β status, presence of an APOE ε4 allele and female sex are key contributors to tau PET positivity, which should aid clinical decision-making and trial designs.

Ossenkoppele, Salvado et al. show that plasma p-tau217 and tau-PET predict cognitive decline equally well among cognitively unimpaired individuals. Their combined use further boosts prognostic accuracy. A sequential approach can enhance precision and efficiency of preclinical Alzheimer trials.

Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role in determining the distribution of tau pathology.

CSF α-synuclein seed amplification assays detect Lewy body pathology accurately but are invasive and costly. Here, the authors show that a two-step workflow using smell-function prescreening maintained 94% accuracy while reducing CSF testing by 43%.

Abnormal amyloid and tau PET in cognitively unimpaired individuals is strongly associated with short-term cognitive decline and subsequent development of dementia.

Plasma eMTBR-tau243 is a specific biomarker of tau tangles in Alzheimer’s disease and enables the detecting and tracking of Alzheimer’s clinical impairment.

Among 1,767 patients in 5 centers, a fully automated blood test showed high accuracy for Alzheimer’s pathology in secondary and primary care using a predefined cutoff.

Cognitively impaired subjects with both Alzheimer’s disease and Lewy body pathology determined using in vivo CSF biomarkers showed faster global cognitive decline and more posterior cortical hypometabolism compared to those with AD pathology only.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Lewy body diseases exhibit notable clinical and pathological heterogeneity. Here, the authors found three distinct trajectories of Lewy body pathology that are associated with different clinicopathological characteristics.

Protein-specific and shared genetic pathways influence the spread of amyloid-β and tau pathology. Hence, distinct gene expression profiles may induce regional vulnerability of the human cortex to the specific proteinopathies of Alzheimer’s disease.

Salvadó et al. developed and validated a CSF-based staging model for sporadic Alzheimer’s disease, which accurately reflects biomarker and clinical changes, enhancing diagnostic and prognostic assessments of participants for clinical setting and trials.

The performance of plasma %p-tau217 is clinically equivalent in classification of Aβ PET status and superior in classification of tau PET status compared to clinically used and FDA-approved CSF tests in cognitively impaired participants.

Individuals with young onset sporadic Alzheimer’s disease show faster pathological and clinical progression. Here the authors report that earlier symptom onset in Alzheimer’s disease is associated with higher tau pathology in globally connected brain hubs, accelerated connectivity-mediated tau spreading and faster cognitive decline.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

CSF MTBR-tau243 is more related to tau tangles and clinical cognitive impairment in Alzheimer’s disease than phospho-tau biomarkers, which are more related to amyloid plaques.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

In Alzheimer disease, the accumulation of amyloid-β (Aβ) is thought to drive both tau pathology and neurodegeneration. In this Review, van der Kant et al. discuss the evidence for Aβ-independent drivers of tau pathology in Alzheimer disease and the implications for therapeutic development.