Biomarkers.

Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: Typical Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but have distinct proteinopathies. AD is characterised by ß-amyloid plaques and intraneuronal neurofibrillary tangles, while LATE is characterised by abnormal neuronal TDP-43 protein. With reference to the prion-like hypothesis regarding the propagation of proteinopathies, investigating white matter fibre bundle alterations could provide new insights into the propagation pathways of specific proteinopathies.

Biomarkers.

Background: The Centiloid framework was developed to harmonize amyloid-PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid-PET scans from the largest "real-world" study of amyloid-PET (IDEAS) and are about to release the data, we aimed to compare the distribution of IDEAS Centiloid values with other available datasets.

Method: In IDEAS, amyloid scans were acquired across 343 facilities and centrally processed at UCSF using a PET-only pipeline.

Biomarkers.

Background: Large-scale studies comparing sporadic early-onset AD (EOAD, age<65) and late-onset AD (LOAD, age≥65) are lacking. We compared amyloid-PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early-Onset AD Study (LEADS) and the Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3).

Method: 731 patients meeting the 2011 NIA-AA criteria for AD dementia or MCI were included (505 early-onset from LEADS, 226 late-onset from ADNI3, Table 1).