The spectrum of Alzheimer's disease.

While hippocampal (H) and inferior parietal lobule (IPL) atrophy are used routinely in Alzheimer's disease (AD) diagnostics, the role of enlarged choroid plexus (ChP) remains unclear. We here examined the AD Neuroimaging Initiative (ADNI) cohort (N=872) to investigate the contribution of enlarged ChP in predicting AD using MRI volumetry. Analyses revealed that no individual volumetric brain changes, nor their combination, can predict AD. Among AD patients, only ~ 19%, 12% and 5% exhibited changes in H, ChP or IPL volumes, while 45% showed no volumetric brain changes at all, not even longitudinally. Amyloid-b peptides, therefore, contribute to brain atrophy and neuronal loss at best only in a subset of amyloid PET-CT positive AD patients. These findings suggest that despite shared amyloidopathy, the observed brain volumetric phenotypes, together with their corresponding cognitive and CSF biomarker profiles, represent unique entities within the AD spectrum much like the synucleinopathies, tauopathies and TDP43-proteinopathies.