Clinicopathological heterogeneity of Alzheimer's disease with pure Alzheimer's disease pathology: Cases associated with dementia with Lewy bodies, very early-onset dementia, and primary progressive aphasia.

We report four cases depicting the heterogeneity of Alzheimer's disease (AD) associated with pure AD pathology. Case 1 was a 77-year-old man with a false positive diagnosis of dementia with Lewy bodies with reduced dopamine transporter uptake activity of the striatum but no Lewy body pathology. There were tau deposits in the large neurons in the putamen, which may be related to the development of parkinsonism. Case 2 was an AD patient in his early 30s who presented with a psychotic episode and a cognitive decline, and later developed myoclonus and seizures. He demonstrated considerable amyloid-beta deposits in the cerebral cortex, including cotton wool plaques, basal ganglia, and cerebellum. Tau deposits were also abundant in the cerebral neocortex, hippocampus, basal ganglia, and brain stem. Case 3 was a 60-year-old woman who exhibited typical symptoms characteristic of the logopenic variant of primary progressive aphasia (lvPPA). Case 4 was a 68-year-old man who exhibited the semantic variant of primary progressive aphasia (svPPA) plus repetition impairment, a rare case associated with AD pathology. In addition to tau pathology, astrocytic pathology was prominent in the white matter and cortical layers of the left temporoparietal cortices. While the main AD lesion in case 4 was evaluated by tau accumulation and astrogliosis in the left temporal lobe, that in case 3 in was evaluated by the same points in the left parietal lobe. Within the spectrum of lvPPA, case 4 may be regarded as a temporal variant of lvPPA presenting svPPA. The pathology of PPA associated with AD may have broader clinical manifestations than that in previously described cases. Case 4 also showed pathological features characteristic of cerebral amyloid angiopathy throughout the cerebral cortex. The distribution of tau and astrocytic pathologies in the cerebral cortex, basal ganglia, brain stem, and cerebellum may explain the various symptoms of atypical pure AD patients.