Argyrophilic Grain Disease: Neuropathology, Frequency in a Dementia Brain Bank and Lack of Relationship with Apolipoprotein E

Togo, Takashi; Cookson, Natalie; Dickson, Dennis W.

doi:10.1111/j.1750-3639.2002.tb00421.x

Cited by 90 publications

(70 citation statements)

References 22 publications

(59 reference statements)

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“…Indeed, the short distances between CBD, PSP, AGD and even the limbic-subcortical type of tau-astrogliopathy of the elderly would support this concept. On the other hand, this would suggest that AGD, CBD, and PSP have some overlapping features as suggested previously [49]. However, our data suggest that they can also be clearly distinguishable based on their hippocampal AT8-IR patterns (see also the heat map, fig.…”

Section: Discussioncontrasting

confidence: 46%

Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias

Milenković

Petrov

Kovács

2014

Dement Geriatr Cogn Disord

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Background/Aims: Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.

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Section: Discussioncontrasting

confidence: 46%

Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias

Milenković

Petrov

Kovács

2014

Dement Geriatr Cogn Disord

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“…The tauopathy was mostly in the medial temporal lobe was consistent with argyrophilic grain disease, a common pathology with increasing age [41]. In contrast, the much younger N167 individual had significant tauopathy consistent with a Braak NFT stage IV.…”

Section: Discussionmentioning

confidence: 84%

Clinical, neuropathological and genotypic variability in SNCA A53T familial Parkinson’s disease

et al. 2008

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Individuals with familial Parkinson's disease (PD) due to a monogenic defect can show considerable clinical and neuropathological variability. To identify factors underlying this variability, histopathological analysis was performed in two clinically different A53T α-synuclein heterozygotes from Family H, a multigenerational α-synuclein A53T kindred. To determine whether additional genetic factors could contribute to phenotypic variability, Family H and another multigenerational A53T kindred were analyzed for parkin polymorphisms. We identified a previously described variant in parkin exon 4 associated with increased PD risk (S167N). The two A53T heterozygotes had markedly different neuropathology and different parkin genotypes: A N167 homozygote had early onset rapidly progressive disease, early dementia, myoclonus and sleep disorder, while a S167 homozygote had late onset, slowly progressive disease and late dementia. Both had brainstem, cortical, and intraneuritic Lewy bodies (LB). The N167 individual had widespread cortical neurofibrillary degeneration, while the S167 individual had only medial temporal lobe neurofibrillary degeneration. The N167 individual had severe neuronal loss in CA2 associated with Lewy neurites (LN), while the S167 individual had severe neuronal loss in CA1 associated with TDP-43 immunoreactive neuronal inclusions. These findings implicate TDP-43 in the pathology of familial PD and suggest that parkin may act as a modifier of the A53T α-synuclein phenotype of familial PD. Furthermore, they suggest a mechanism by which a rare genetic variant that is associated with a minor increase of PD risk in the heterozygous state may, in the homozygous state, exacerbate a disease phenotype associated with a highly penetrant dominant allele.

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“…18 The prevalence in unselected necropsy series of approximately 5% 18 is similar to results obtained from series of dementia cases. 19 AGD is found in significantly higher proportions in neurodegenerative series, ranging from 33% to 40%. 17 Other neurodegenerative disorders associated with AGD include dementia with Lewy bodies (DLB) and MSA.…”

Section: Discussionmentioning

confidence: 94%