Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases
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We describe three cases of early- (cases 1–3, 28–39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Aβ42 was deposited more predominantly than Aβ40 in three cases. However, in case 2, approximately twice as much Aβ40 as Aβ42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. α-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Aβ component of AD amyloid (NAC), a central fragment of α-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Aβ40 and Aβ42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Aβ deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving α-synuclein and NAC deposition.