Astrocytic tau pathologies in aged human brain

Okamoto, Koichi; Amari, Masakuni; Fukuda, Toshio; Suzuki, Keiji; Takatama, Masamitsu

doi:10.1111/neup.12544

Cited by 13 publications

(14 citation statements)

References 25 publications

(95 reference statements)

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“…We re-examined senile changes in approximately 400 autopsied brains stored at our institute. 22 Autopsies were performed in accordance with established procedures. Samples were used in this study after obtaining informed consent from the family of each patient.…”

Section: Methodsmentioning

confidence: 99%

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Amyloid‐β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly

Okamoto¹,

Amari²,

Fukuda³

et al. 2020

Neuropathology

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We examined 29 cases in which cerebral amyloid angiopathy (CAA) was detected among routine aged autopsies. Most cases with severe CAA had many amyloid-β (Aβ) plaques in the occipital cortex. Nonetheless, two cases had few Aβ plaques with many small vessels and capillaries with CAA. In the two cases, severe CAA was widely distributed, except in the frontal lobes. Aβ deposits in capillaries often showed the characteristic pattern of dysphoric amyloid angiopathy. A few naked plaques were present. Although Aβ plaques were sparse near small vessels with CAA, there were many Aβ plaques distant from small vessels with CAA. Some of the remaining plaques had a moth-eaten appearance. Based on Aβ-positive star-like appearance and results of double immunohistochemistry for glial fibrillary acidic protein and Aβ 1-42 , some astrocytes appeared to contain Aβ. Ionized calcium-binding adapter molecule 1 (Iba1)-positive microglia were scattered within the neuropil, with some present around small vessels with CAA. Iba1-positive microglia also seemed to phagocytose Aβ in several senile plaques by double immunostaining. Neurons and neurites identified with a monoclonal antibody against phosphorylated tau (clone AT8) were occasionally detected in sparse plaque areas, with AT8-identified dot-like structures present around capillaries with CAA. Accumulation of T lymphocytes was detected around vessels in the subarachnoid space in one case. The morphological changes detected in our two cases were similar to those of morphological markers of plaque clearance after Aβ immunotherapy. Nonetheless, our cases did not receive Aβ immunotherapy, but similar pathologies were observed. Overall, advanced CAA cases, including our two cases, may be examples of plaque clearance without Aβ immunotherapy. Further studies are needed to resolve the mechanism of Aβ plaque clearance using these cases.

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Section: Methodsmentioning

confidence: 99%

“…We re‐examined senile changes in approximately 400 autopsied brains stored at our institute . Autopsies were performed in accordance with established procedures.…”

Section: Methodsmentioning

confidence: 99%

Amyloid‐β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly

Okamoto¹,

Amari²,

Fukuda³

et al. 2020

Neuropathology

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“…The latter is distributed primarily in white and gray matter, in subpial and subependimal locations and at the perivascular BBB ( Figure 1 ). Among ARTAG properties are the tau sites of their phosphorylation, partially different from those of neurons, combined with interactions with other phosphorylated proteins [ 70 , 71 , 72 , 73 ]. On the other hand, a fraction of ARTAG astrocytes, associated with the primary progressive aphasia phenotype of the AD cohort, correlates with older ages [ 73 , 74 ], while primary astrocytes are distributed more widely than ARTAG astrocytes.…”

Section: Tau and Tauopathiesmentioning

confidence: 99%

“…Among ARTAG properties are the tau sites of their phosphorylation, partially different from those of neurons, combined with interactions with other phosphorylated proteins [ 70 , 71 , 72 , 73 ]. On the other hand, a fraction of ARTAG astrocytes, associated with the primary progressive aphasia phenotype of the AD cohort, correlates with older ages [ 73 , 74 ], while primary astrocytes are distributed more widely than ARTAG astrocytes. Among their functions is the conversion of novel insights into brain aging and neurodegenerative diseases [ 70 , 71 ].…”

Section: Tau and Tauopathiesmentioning

confidence: 99%

Astrocytes: News about Brain Health and Diseases

Meldolesi

2020

Biomedicines

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Astrocytes, the most numerous glial cells in the brains of humans and other mammalian animals, have been studied since their discovery over 100 years ago. For many decades, however, astrocytes were believed to operate as a glue, providing only mechanical and metabolic support to adjacent neurons. Starting from a “revolution” initiated about 25 years ago, numerous astrocyte functions have been reconsidered, some previously unknown, others attributed to neurons or other cell types. The knowledge of astrocytes has been continuously growing during the last few years. Based on these considerations, in the present review, different from single or general overviews, focused on six astrocyte functions, chosen due in their relevance in both brain physiology and pathology. Astrocytes, previously believed to be homogeneous, are now recognized to be heterogeneous, composed by types distinct in structure, distribution, and function; their cooperation with microglia is known to govern local neuroinflammation and brain restoration upon traumatic injuries; and astrocyte senescence is relevant for the development of both health and diseases. Knowledge regarding the role of astrocytes in tauopathies and Alzheimer’s disease has grow considerably. The multiple properties emphasized here, relevant for the present state of astrocytes, will be further developed by ongoing and future studies.

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“…Thorn shaped astrocytes in subpial, subependymal, and perivascular areas indicate astrocytic tau pathologies in aged human brain (Okamoto et al 2019). Extravascular fibrinogen in the cerebrospinal fluid of elderly population is indicative of cerebral atherosclerotic small vessel diseases (McAleese et al 2019).…”

Section: Ageing and Brain Vascular Pathologymentioning

confidence: 99%

Sleep, brain vascular health and ageing

et al. 2020

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Sleep maintains the function of the entire body through homeostasis. Chronic sleep deprivation (CSD) is a prime health concern in the modern world. Previous reports have shown that CSD has profound negative effects on brain vasculature at both the cellular and molecular levels, and that this is a major cause of cognitive dysfunction and early vascular ageing. However, correlations among sleep deprivation (SD), brain vascular changes and ageing have barely been looked into. This review attempts to correlate the alterations in the levels of major neurotransmitters (acetylcholine, adrenaline, GABA and glutamate) and signalling molecules (Sirt1, PGC1α, FOXO, P66 shc , PARP1) in SD and changes in brain vasculature, cognitive dysfunction and early ageing. It also aims to connect SD-induced loss in the number of dendritic spines and their effects on alterations in synaptic plasticity, cognitive disabilities and early vascular ageing based on data available in scientific literature. To the best of our knowledge, this is the first article providing a pathophysiological basis to link SD to brain vascular ageing.

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Astrocytic tau pathologies in aged human brain

Cited by 13 publications

References 25 publications

Amyloid‐β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly

Amyloid‐β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly

Astrocytes: News about Brain Health and Diseases

Sleep, brain vascular health and ageing

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