Neuropathology of preclinical and clinical lateonset Alzheimer's disease

We report on the neuropathological examinations of a 74‐year‐old woman with Alzheimer's disease (AD) and of her 47‐year‐old nondementd daughter. The brain of the mother showed fully developed pathological changes of AD. By contrast, the brain of the daughter revealed only perineuronal deposition of diffuse amyloid in cerebral cortex and striking abnormalities of the endosomallysosomal system, without neurofibrillary, glial, or microglial changes. These observations suggest that amyloid deposition and endosomal‐lysosomal changes are early events in late‐onset AD and that they may precede the onset of dementia of several decades.