Alzheimer’s Disease: Etiology, Neuropathology and Pathogenesis DOI Creative Commons
Olivia Sheppard, Michael P. Coleman

Exon Publications eBooks, Год журнала: 2020, Номер unknown, С. 1 - 22

Опубликована: Дек. 18, 2020

Alzheimer's disease is the most common form of dementia and neurodegenerative disease. It manifests as a decline in short-term memory cognition that impairs daily behavior. Most cases are sporadic, but small minority inherited forms allow gene identification which, together with neuropathology, yields important clues about wider causes. Environmental metabolic risk factors, including inflammation vascular impairment, play role onset progression. While neuronal atrophy loss synapses occur throughout cerebral cortex, we lack full understanding how this arises. The known hallmarks include amyloid-β plaques neurofibrillary tau tangles while extensive research has been carried out past few decades, exact these protein aggregates remains elusive. In chapter, discuss mechanisms have implicated, inflammation, mitochondrial dysfunction, oxidative stress changes clearance.

Язык: Английский

Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia DOI Creative Commons
C. Anders Olson, Alonso J. Iñiguez, Grace Yang

и другие.

Cell Host & Microbe, Год журнала: 2021, Номер 29(9), С. 1378 - 1392.e6

Опубликована: Авг. 5, 2021

Язык: Английский

Процитировано

93
White matter capillaries in vascular and neurodegenerative dementias DOI Creative Commons
Yoshiki Hase,

Ren Ding,

Gina L. Harrison

и другие.

Acta Neuropathologica Communications, Год журнала: 2019, Номер 7(1)

Опубликована: Фев. 7, 2019

Previous studies suggest white matter (WM) integrity is vulnerable to chronic hypoperfusion during brain ageing. We assessed ~ 0.7 million capillary profiles in the frontal lobe WM across several dementias comprising Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular mixed dementias, post-stroke as well no and similar age ageing young controls without significant pathology. Standard histopathological methods were used determine microvascular pathology width densities 153 subjects using markers of basement membrane (collagen IV; COL4) endothelium (glucose transporter-1; GLUT-1). Variable including coiled, tortuous, collapsed degenerated capillaries occasional microaneurysms was present all dementias. As expected, 20–49% lower than overlying cortex. This differential density between cortex clearly demonstrated by COL4, which highly correlated GLUT-1 (Spearman's rho = 0.79, P 0.000). COL4 immunopositive decreased 18% neurodegenerative However, we found increased 57% versus other Using three different measure diameters, be significantly wider 19–45% compared those neocortex apparent both GLUT-1. Remarkably, widths 20% (P < 0.01). also noted mean scores incorporating myelin loss, arteriolosclerosis perivascular spacing (Pearson's r 0.71, 0.032). Our key finding indicates that are but they dilate further pathogenesis. undergo restructuring deep reflects compensatory changes retain perfusion hypoperfusive states ageing-related

Язык: Английский

Процитировано

87
Emerging Biomarkers in Vascular Cognitive Impairment and Dementia: From Pathophysiological Pathways to Clinical Application DOI Open Access
Virginia Cipollini, Fernanda Troili, Franco Giubilei

и другие.

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(11), С. 2812 - 2812

Опубликована: Июнь 8, 2019

Vascular pathology is the second most common neuropathology of dementia after Alzheimer’s disease (AD), with small vessels (SVD) being considered major cause vascular cognitive impairment and (VCID). This review aims to evaluate pathophysiological pathways underlying a diagnosis VCID. Firstly, we will discuss role endothelial dysfunction, blood-brain barrier disruption neuroinflammation in its pathogenesis. Then, analyse different biomarkers including ones inflammatory responses central nervous system tissue injuries, coagulation thrombosis circulating microRNA. Evidences on peripheral for VCID are still poor large-scale, prospectively designed studies needed translate these findings into clinical practice, order set combinations use differential among types dementia.

Язык: Английский

Процитировано

83
Vascular Hypothesis of Alzheimer Disease DOI Open Access
Sanny Scheffer, Dorien M. A. Hermkens, Louise van der Weerd

и другие.

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2021, Номер 41(4), С. 1265 - 1283

Опубликована: Фев. 25, 2021

Alzheimer disease (AD) is marked by profound neurodegeneration, neuroinflammation, and cognitive decline. Pathologically, AD characterized the accumulation of extracellular amyloid intraneuronal tangles, consisting hyperphosphorylated tau. To date, factors leading to onset progression are still an important topic investigation. Various epidemiological studies revealed cardiovascular as contributor development AD, so-called vascular hypothesis. Vascular risk factors, such hypertension, diabetes, hyperhomocysteinemia, associated with a significantly increased chance developing suggesting additive or even synergistic effect. These often linked reduction in cerebral blood flow resulting chronic hypoperfusion suggested play key role AD. However, causal effects for remain largely unknown. Evidence from animal support that induction causes strong aggravation AD-related pathology, but comprehensive overview how various contribute lacking. Therefore, we here critically review current literature, unravel existing evidence derived vivo mouse define development. We conclude that, although many aspects hypothesis well supported observational studies, in-depth mechanistic well-designed randomized controlled trials highly needed establish temporal relationships. Described new insights can have major prospective potential therapeutic interventions.

Язык: Английский

Процитировано

72
Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function DOI Creative Commons
Qian Liu, Mohammad Iqbal H. Bhuiyan, Ruijia Liu

и другие.

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Авг. 28, 2021

Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na + /H exchanger-1 (NHE1) reactive astrocytes astrocytic hypertrophy swelling. In this study, we examined role NHE1 protein astrogliosis, demyelination, function a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice receiving vehicle selective inhibitor HOE642 were monitored for changes regional blood flow behavioral performance 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury demyelination. Astrogliosis demyelination further by immunofluorescence staining. Astrocytic transcriptional profiles analyzed bulk RNA-sequencing RT-qPCR. Results reduction spatial working memory deficits detected mice, along significantly reduced mean fractional anisotropy (FA) values corpus callosum, external capsule, hippocampus MRI DTI analysis. Compared sham control displayed axonal increased GFAP Iba1 microglia. Pharmacological inhibition its prevented BCAS-induced gliosis, tracts hippocampus, improved performance. Transcriptome immunostaining analysis revealed that specifically attenuated pro-inflammatory pathways NADPH oxidase activation. Conclusion Our study demonstrates involved transformation induced CCH, blockade has potentials reducing impairment.

Язык: Английский

Процитировано

60
A Study on the Pathogenesis of Vascular Cognitive Impairment and Dementia: The Chronic Cerebral Hypoperfusion Hypothesis DOI Open Access
Weiwei Yu, Yao Li, Jun Hu

и другие.

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(16), С. 4742 - 4742

Опубликована: Авг. 14, 2022

The pathogenic mechanisms underlying vascular cognitive impairment and dementia (VCID) remain controversial due to the heterogeneity of causes complexity disease neuropathology. However, one common feature shared among all these is cerebral blood flow (CBF) dysregulation, chronic hypoperfusion (CCH) universal consequence CBF which subsequently results in an insufficient supply brain, ultimately contributing VCID. purpose this comprehensive review emphasize important contributions CCH VCID illustrate current findings about involved CCH-induced pathological changes. Specifically, evidence mainly provided support molecular mechanisms, including Aβ accumulation, inflammation, oxidative stress, blood-brain barrier (BBB) disruption, trophic uncoupling white matter lesions (WMLs). Notably, there are close interactions multiple further research necessary elucidate hitherto unsolved questions regarding interactions. An enhanced understanding features preclinical models could provide a theoretical basis, achieving shift from treatment prevention.

Язык: Английский

Процитировано

45
Melatonin improves cognitive function by suppressing endoplasmic reticulum stress and promoting synaptic plasticity during chronic cerebral hypoperfusion in rats DOI

Phakkawat Thangwong,

Pranglada Jearjaroen,

Piyarat Govitrapong

и другие.

Biochemical Pharmacology, Год журнала: 2022, Номер 198, С. 114980 - 114980

Опубликована: Фев. 24, 2022

Язык: Английский

Процитировано

43
The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease DOI Creative Commons
Yu Tian,

Mengxi Zhao,

Yiyi Chen

и другие.

Biomolecules, Год журнала: 2022, Номер 12(6), С. 748 - 748

Опубликована: Май 25, 2022

There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) the main contributor to VCI. Several potential physiopathologic mechanisms have been proven be involved in process CSVD, such as blood-brain barrier damage, vessels stiffening, venous collagenosis, blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin subsequent neurodegeneration. However, there still limited overall understanding sequence relative importance these mechanisms. The glymphatic system (GS) meningeal lymphatic (mLVs) are analogs central nervous (CNS). As such, systems play critical roles regulating cerebrospinal fluid (CSF) interstitial (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence played vital animal models CSVD patients with CSVD. Given complexity it was significant understand underlying interaction between transport Here, we provide novel framework based on new advances four aspects, including risk factors, mechanisms, clinical subtypes, cognition, which aims explain how contribute progression proposes comprehensive insight into therapeutic strategy

Язык: Английский

Процитировано

43
Association of small vessel disease with tau pathology DOI Creative Commons
Alifiya Kapasi, Lei Yu, Vladislav Petyuk

и другие.

Acta Neuropathologica, Год журнала: 2022, Номер 143(3), С. 349 - 362

Опубликована: Янв. 19, 2022

Abstract Emerging evidence suggests that small vessel disease (SVD) is a risk factor for clinical dementia and may contribute to AD neuropathological changes. Watershed brain regions are located at the most distal areas between arterial territories, making them vulnerable SVD-related We examined association of pathologic markers SVD, specifically arteriolosclerosis in watershed regions, with Participants ( N = 982; mean age-at-death 90; 69% women) were enrolled as part one two cohort studies aging dementia. At autopsy, evaluation included semi-quantitative grading pathology from 2 cortical regions: anterior (AWS) posterior (PWS), densities β-amyloid tau-tangle pathology, other common age-related pathologies. Linear regression models burden. In follow-up analyses, available ex-vivo MRI proteomics data subset decedents leveraged examine whole measure WMH, presumed marker burden, well proteomic tau. was common, 45% older persons having moderate-to-severe AWS region, 35% PWS. fully adjusted controlled demographics pathologies, an increase severity PWS associated higher burden neocortical tau but not β-amyloid. or pathology. Ex-vivo WMH greater Furthermore, abundance phosphopeptides, promote formation aggregates. These provide compelling linked pathological changes brain.

Язык: Английский

Процитировано

40
A brief overview of a mouse model of cerebral hypoperfusion by bilateral carotid artery stenosis DOI
Hidehiro Ishikawa, Akihiro Shindo,

Akane Mizutani

и другие.

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2023, Номер 43(2_suppl), С. 18 - 36

Опубликована: Март 8, 2023

Vascular cognitive impairment (VCI) refers to all forms of disorder related cerebrovascular diseases, including vascular mild impairment, post-stroke dementia, multi-infarct subcortical ischemic dementia (SIVD), and mixed dementia. Among the causes VCI, more attention has been paid SIVD because causative cerebral small vessel pathologies are frequently observed in elderly people gradual progression decline often mimics Alzheimer’s disease. In most cases, diseases accompanied by hypoperfusion. mice, prolonged hypoperfusion is induced bilateral carotid artery stenosis (BCAS) with surgically implanted metal micro-coils. This BCAS model was proposed as a mouse 2004, spreading use this provided novel data regarding dysfunction histological/genetic changes Oxidative stress, microvascular injury, excitotoxicity, blood-brain barrier dysfunction, secondary inflammation may be main mechanisms brain damage due hypoperfusion, some potential therapeutic targets for have using transgenic mice or clinically used drugs studies. review article overviews findings from studies that hypoperfused-SIVD model, which were published between 2004 2021.

Язык: Английский

Процитировано

25