1/5. A novel mutation (G217D) in the Presenilin 1 gene ( PSEN1) in a Japanese family: presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum.We report a family of Japanese origin that has five individuals from two generations affected by an illness characterized by dementia, a stooped posture and an antiflexion gait with an onset in the fourth or fifth decade of life. Two siblings had a clinical phenotype characterized by dementia and Parkinsonism with stooped posture, rigidity and bradykinesia. Neuropathological alterations in both patients included numerous 'cotton wool' plaques (CWPs), senile plaques, severe amyloid angiopathy, neurofibrillary tangles, neuronal rarefaction and gliosis. CWPs were present throughout the cerebral cortex as well as in the caudate nucleus, putamen, claustrum, thalamus, substantia innominata and colliculi. These plaques contained a small quantity of argyrophilic and tau-immunopositive neurites as well as glial fibrillary acidic protein-immunopositive elements. They were mildly fluorescent with thioflavin S and immunopositive using monoclonal antibodies recognizing amyloid beta (A beta) ending at residue 42. The main constituents of CWPs were neuropil elements and extracellular amyloid fibrils. These neuropil elements were small dendrites including spines, axon terminals containing synaptic vesicles and astrocytic processes. dendrites occasionally contained bundles of paired helical filaments. dendrites and axons often had an irregular outline and appeared as degenerating osmiophilic processes containing electron-dense mitochondria. Genetic analysis of the proband's affected sibling revealed a novel nucleotide substitution (G to A) in exon 8 of the Presenilin 1 ( PSEN1) gene. This nucleotide change results in a glycine to aspartic acid substitution at residue 217 of the PSEN1 protein. This study provides further evidence of clinical and pathological heterogeneity in dementing illnesses associated with PSEN1 mutations.- - - - - - - - - - ranking = 1keywords = cotton (Clic here for more details about this article) |
2/5. presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities.The authors report unusual presentations of members of an Irish family with familial AD due to an E280G mutation in exon 8 of presenilin-1. One had spastic paraparesis and white matter abnormalities on cranial MRI. A sibling had an internuclear ophthalmoplegia, spastic-ataxic quadriparesis, and "cotton-wool plaques" with amyloid angiopathy on brain biopsy. Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels.- - - - - - - - - - ranking = 0.2keywords = cotton (Clic here for more details about this article) |
3/5. Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases.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 Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-synuclein-positive lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-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 Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta 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 alpha-synuclein and NAC deposition.- - - - - - - - - - ranking = 1keywords = cotton (Clic here for more details about this article) |
4/5. A mutant PSEN1 causes dementia with lewy bodies and variant Alzheimer's disease.We report early-onset parkinsonism and dementia of 18 years' duration in a 52-year-old man whose grandfather and father had suffered from a similar neurological disease. In this patient, we found neuronal loss in various brain regions including the substantia nigra and cerebral cortex, lewy bodies, cotton wool plaques, corticospinal tract degeneration, cerebral amyloid angiopathy, and a novel three-base pair deletion in exon 12 of the presenilin-1 (PSEN1) gene. We considered that the mutant PSEN1 might play an important role in the pathogenetic process of both aggregation of alpha-synuclein into lewy bodies and deposition of beta-amyloid into cotton wool plaques.- - - - - - - - - - ranking = 0.4keywords = cotton (Clic here for more details about this article) |
5/5. A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples of the delta9 variant, the deletion was not caused by a splice acceptor site mutation.- - - - - - - - - - ranking = 0.2keywords = cotton (Clic here for more details about this article) |