Argyrophilic grain disease (AGD) is a frequent late-onset, 4-repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects ≥50 years of age from Sao Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 ± 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases.

/pdf/argyrophilic-grain-disease-demographics-clinical-and-1pm5ta8q5z.pdf

Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study

Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems The brains of patients with LBD often display other comorbid pathologies, ie insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD) The incidence and physiological relevance of these concurrent pathological findings remain controversial We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies) APOE and MAPT genetic variants were also investigated A majority of LBD cases had 2 or 3 concomitant findings, particularly Alzheimer disease-related pathology Pathological stages of tau, β-amyloid and α-synuclein pathologies were increased in cases with dementia Aβ score was the best correlate of the time to dementia in PD In addition, β-amyloid deposition correlated with α-synuclein load in all groups MAPT H1 haplotype did not influence any assessed pathology in PD These results highlight the common concurrence of pathologies in patients with LBD that may have an impact on the clinical expression of the diseases

/pdf/regional-overlap-of-pathologies-in-lewy-body-disorders-pic3d9q2qm.pdf

Regional Overlap of Pathologies in Lewy Body Disorders.

http://diposit.ub.edu/dspace/bitstream/2445/135838/1/689436.pdf

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner.

Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. AGD diagnosis can only be achieved postmortem based on the finding of its three main pathologic features: argyrophilic grains, oligodendrocytic coiled bodies and neuronal pretangles. AGD is frequently seen together with Alzheimer's disease-type pathology or in association with other neurodegenerative diseases. Recent studies suggest that AGD may be a defense mechanism against the spread of other neuropathological entities, particularly Alzheimer's disease. This review aims to provide an in-depth overview of the current understanding on AGD.

/pdf/argyrophilic-grain-disease-an-underestimated-tauopathy-2pp035bv68.pdf

Argyrophilic grain disease: An underestimated tauopathy

Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. Three main clinical variants are widely recognized within the FTLD spectrum: the behavioural variant of frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). FTLD represents a highly heterogeneous group of neurodegenerative disorders which are best classified according to the main protein component of pathological neuronal and glial inclusions. The most common pathological class of FTLD is associated with the TDP-43 protein (FTLD-TDP), while FTLD-Tau is considered slightly less common while the FTLD-FUS (Fused in sarcoma protein) pathology is rare. In this review, these three major pathological types of FTLD are discussed.

/pdf/neuropathology-of-frontotemporal-lobar-degeneration-a-review-4lqqq5zxak.pdf

Neuropathology of frontotemporal lobar degeneration: a review.

Tau-positive grains are constant in centenarians' hippocampus.

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Tau-positive grains are constant in centenarians' hippocampus.