Parkinson Disease Neuropathological Comorbidities: Prevalences from Younger-Old to Older-Old, With Comparison to Non-Demented, Non-Parkinsonian Subjects

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract Co-existing neuropathological comorbidities have been repeatedly reported to be extremely common in subjects dying with dementia due Alzheimer disease. As these are likely additive cognitive impairment, and may not affected by molecularly-specific AD therapeutics, they cause significant inter-individual response heterogeneity amongst clinical trials. Furthermore, while originally noted for the oldest old, recent reports now documented high comorbidity prevalences younger old subjects, who more included Comorbid neuropathologies Parkinson disease received much less attention. AD, interfere evaluation of PD We here examined decadal-wise presence multiple co-pathologies, their effects, a series autopsies control from Arizona Study Aging Neurodegenerative Disorders. Amyloid plaques were present than 40% patients 60s, 85% those 90s. Neurofibrillary tangles PD, as all elderly humans, 60s onwards, Braak tangle stages IV or greater, which strongly associated severe reached 40%, 50% 60% 70s, 80s 90s, respectively. Both predictors lower MMSE score greater CAA scores had borderline significance. None these, however, independently higher UPDRS score. The ApoE4 allele, known predictor pathology, especially amyloid plaques, was an independent function either measures, suggesting that its influence is largely mediated it predisposes to. Non-AD tauopathies, including major conditions progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), well microscopic changes argyrophilic grains (ARG) aging-related tau astrogliopathy (ARTAG), also co-existed ARG ARTAG, ranged between 20% across decades former up 80% latter; we did find associations final scores. failed association limbic TDP-43 histopathology motor but our heavily weighted prior studies correlate, limited score, missed domain subsets. found several cerebrovascular pathologies both brain infarcts, circle Willis atherosclerosis, white matter rarefaction All investigated pathology types non-demented, non-parkinsonian increased age parallel co-existing generally prevalences. concurrence rate neurodegenerative protein aggregate diseases suggestive synergistic co-pathogenesis, where one type instigate accelerate another type, underlying predisposing physiological molecular mechanisms.

Язык: Английский

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Multiple Neuropathologies Underly Hippocampal Subfield Atrophy in a Case With a Slowly Progressive Amnestic Syndrome: Challenging the Notion of Pure LATE‐NC

Neuropathology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

ABSTRACT Alzheimer's disease (AD) is the leading cause of dementia in elderly, marked by abnormal protein buildup (beta‐amyloid and tau) resulting neuronal loss, especially medial temporal lobe other limbic regions. The presence transactive response DNA binding 43 (TDP‐43) immunoreactive inclusions regions has also been associated with neuroimaging changes It proposed that hypometabolism on [ 18 F] fluorodeoxyglucose positron emission tomography (FDG‐PET) a patient slowly evolving amnestic syndrome may be signature TDP‐43. In this context, we observed an 86‐year‐old Caucasian female characterized syndrome, along focal atrophy evident MRI FDG‐PET. subsequently died underwent autopsy. We performed detailed digital neuropathological analyses hippocampal subfields to better understand relationship between clinico‐imaging findings histopathology. addition TDP‐43, identified three pathological processes lobe: sequestosome‐1/p62, argyrophilic grain (AGD), primary age‐related tauopathy (PART). Hippocampal subfield volumes rates were no different from those matched healthy controls, except for rate cornu ammonis 1 (CA1). Digital histopathology revealed relative highest burden pathology p62, followed AGD, PART CA1. Multiple appear have contributed our progressive syndrome.

Язык: Английский

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Tau biomarkers for Neurodegenerative Diseases: current state and perspectives

Parkinsonism & Related Disorders, Год журнала: 2025, Номер unknown, С. 107772 - 107772

Опубликована: Март 1, 2025

Язык: Английский

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Argyrophilic Grain Disease Clinically Presenting as Progressive Supranuclear Palsy with Progressive Gait Freezing

Movement Disorders Clinical Practice, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Abstract Background Argyrophilic grain disease (AGD) is a four‐repeat tauopathy characterized by the accumulation of argyrophilic grains. Its primary clinical manifestation late‐onset amnestic dementia. While extension grains to substantia nigra may be related its potential association with parkinsonism, biochemical analyses are lacking. Objectives To elucidate extent AGD midbrain, including nigra, using histopathological examination and analysis in pathologically proven case presenting parkinsonism cognitive impairment. Methods We describe patient suggestive progressive supranuclear palsy. Neuropathological investigations were performed. Results Neurological an 80‐year‐old man 6‐year history gait disturbance revealed freezing, postural instability, bradykinesia, The was diagnosed palsy freezing. Five years later, reported falling backward repeatedly, became wheelchair‐bound, died pneumonia. Macroscopic observations marked amygdala atrophy. Microscopic findings limbic system, compatible Saito stage III, as well midbrain tegmentum. Western blotting showed AGD‐specific band pattern, immunoelectron microscopy tau filament abnormally phosphorylated both nucleus accumbens midbrain. Conclusions This report further confirmed that presents commensurate pathology extending Therefore, should considered differential diagnosis cases impairment older population.

Язык: Английский

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Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change

Acta Neuropathologica, Год журнала: 2025, Номер 149(1)

Опубликована: Апрель 26, 2025

Язык: Английский

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Argyrophilic grain disease

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 209 - 214

Опубликована: Янв. 1, 2025

Язык: Английский

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