Cotton Wool Plaques in Non-Familial Late-Onset Alzheimer Disease

Abstract

Cotton wool plaques (CWP) are large, ball-like plaques lacking dense amyloid cores that displace adjacent structures. They were first described in a Finnish kindred with early-onset Alzheimer disease (AD) with spastic paraparesis due to a presenilin-1 delta9 mutation. We describe a case of sporadic late-onset AD with numerous neocortical CWP as well as severe amyloid angiopathy and marked leukoencephalopathy, compared with 16 cases of late-onset AD with similar degrees of amyloid angiopathy and leukoencephalopathy. The cases were studied with histologic methods and with single and double immunostaining for beta-amyloid (Abeta), paired helical filaments-tau (PHF-tau), neurofilament (NF), glial fibrillary acidic protein (GFAP), HLA-DR, and amyloid precursor protein (APP). We found that CWP were well-circumscribed amyloid deposits infiltrated by ramified microglia and surrounded by dystrophic neurites that were immunopositive for APP, but only weakly for NF and PHF-tau. Abeta1-12 was diffuse throughout the CWP, while Abeta37-42 was peripherally located and Abeta20-40 more centrally located. Two of the 16 late-onset AD cases also had CWP, but they were also admixed with diffuse plaques and plaques with dense amyloid cores. Pyramidal tract degeneration was not a consistent finding or a prominent feature in any case. The results suggest that CWP are not specific for early-onset familial AD with spastic paraparesis.

Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies

“…Once those time and space determinants have been taken into account, there are no peculiar aspects that could distinguish types of deposits specific to a given "strain" of Aβ-with the sole exception of cotton-wool plaques. Cotton-wool plaques, homogeneous and Congo red negative, have a distinct aspect; they were initially described in FAD caused by the deltaE9 PS1 mutation, and are also rarely found in sporadic cases [77]. To our knowledge, there has been no attempt to seed the pathology in tg mice with homogenates of cerebral cortex containing this type of plaque.…”

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

“…In a review of 5 Japanese and 9 Caucasian cases with spastic paraparesis and CWP, Tabira et al [161] found evidence for extremely high Aβ42 production, with CWP seen in basal ganglia, brainstem and even spinal cord. However, CWP are not unique to PSEN1 EOAD as they may also be seen in sporadic LOAD [98].…”

Unraveling the genes implicated in Alzheimer's disease

“…Mutations in PSEN1 (AD3) and PSEN2 (AD4) were reported to increase the production of Aβ, which results in a larger production of Aβ42 than Aβ40, and Aβ42 tends to be more amyloidogenic and aggregates more easily than Aβ40 (8). PSEN1 mutations may also be associated with cotton wool plaques (9). PSEN2 has a very similar structure and function to PSEN1.…”