scholarly journals Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold

2018 ◽  
Author(s):  
Benjamin Falcon ◽  
Wenjuan Zhang ◽  
Manuel Schweighauser ◽  
Alexey G. Murzin ◽  
Ruben Vidal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
Paired Helical Filaments ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Posterior Cortical Atrophy ◽  
Negative Stain ◽  
Negative Stain Electron Microscopy ◽  
Ordered Assembly

AbstractThe ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer’s disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of typical AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of typical AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for a case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament structure. The immuno-EM findings, which established the presence of repeats 3 and 4, but not repeats 1 and 2, of tau in the filament cores of all AD cases and brain regions thereof, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.

Difficulties in diagnosing atypical variants of Alzheimer’s disease

2021 ◽  
Vol 26 (5) ◽  
pp. 16-23
Author(s):  
A. A. Tappakhov ◽  
T. Ya. Nikolaeva ◽  
T. E. Popova ◽  
N. A. Shnayder
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Picture ◽  
Short Term Memory ◽  
Late Onset ◽  
Early Stage ◽  
Primary Progressive Aphasia ◽  
Cortical Atrophy ◽  
Posterior Cortical Atrophy ◽  
Short Term

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

O4-03-06: Effects of cortical visual impairment on navigational ability in posterior cortical atrophy and typical Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_6) ◽  
pp. P274-P274 ◽  
Author(s):  
Keir X.X. Yong ◽  
Catherine Holloway ◽  
Amelia Carton ◽  
Biao Yang ◽  
Tatsuto Suzuki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Impairment ◽  
Cortical Atrophy ◽  
Posterior Cortical Atrophy ◽  
Cortical Visual Impairment

scholarly journals Posterior cortical atrophy: A rare variant of Alzheimer’s disease

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Michael A. Meyer ◽  
Stephen A. Hudock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Photon Emission ◽  
Occipital Cortex ◽  
Cortical Atrophy ◽  
Emission Computed Tomography ◽  
Posterior Cortical Atrophy ◽  
Homonymous Hemianopsia

Posterior cortical atrophy is a rare condition first described in 1988 involving progressive degeneration and atrophy of the occipital cortex, often recognized after an unexplained homonymous hemianopsia may be discovered. We report a case in association with Alzheimer’s disease in a 77-year-old female, who underwent brain single-photon emission computed tomography as well brain positron emission tomography using Florbetapir to further evaluate progressive cognitive decline. The patient had also been followed in Ophthalmology for glaucoma, where a progressive unexplained change in her visual field maps were noted over one year consistent with a progressive right homonymous hemianopsia. This rare combination of findings in association with her dementia led to a detailed review of all her imaging studies, concluding with the surprising recognition for a clear hemi-atrophy of the primary left occipital cortex was occurring, consistent with Alzheimer’s disease affecting the primary visual cortex. Further awareness of this disease pattern is needed, as Alzheimer’s disease typically does not affect the primary visual cortex; other conditions to consider in general include Lewy Body dementia, cortico-basal degeneration and prion disease.

scholarly journals Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer’s disease

2018 ◽  
Vol 115 (6) ◽  
pp. E1289-E1298 ◽  
Author(s):  
Rachel E. Bennett ◽  
Ashley B. Robbins ◽  
Miwei Hu ◽  
Xinrui Cao ◽  
Rebecca A. Betensky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Blood Vessel ◽  
Cell Biology ◽  
The Elderly ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Vascular Abnormalities ◽  
Alzheimer Pathology

Mixed pathology, with both Alzheimer’s disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer’s disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain’s microvasculature.

scholarly journals Cortical Microstructural Alterations in Mild Cognitive Impairment and Alzheimer’s Disease Dementia

2020 ◽  
Vol 30 (5) ◽  
pp. 2948-2960 ◽  
Author(s):  
Nicholas M Vogt ◽  
Jack F Hunt ◽  
Nagesh Adluru ◽  
Douglas C Dean ◽  
Sterling C Johnson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cortical Thickness ◽  
Gray Matter ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Microstructural Alterations ◽  
Additional Information

Abstract In Alzheimer’s disease (AD), neurodegenerative processes are ongoing for years prior to the time that cortical atrophy can be reliably detected using conventional neuroimaging techniques. Recent advances in diffusion-weighted imaging have provided new techniques to study neural microstructure, which may provide additional information regarding neurodegeneration. In this study, we used neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model, in order to investigate cortical microstructure along the clinical continuum of mild cognitive impairment (MCI) and AD dementia. Using gray matter-based spatial statistics (GBSS), we demonstrated that neurite density index (NDI) was significantly lower throughout temporal and parietal cortical regions in MCI, while both NDI and orientation dispersion index (ODI) were lower throughout parietal, temporal, and frontal regions in AD dementia. In follow-up ROI analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) within the same brain regions, differences in NODDI metrics remained, even after controlling for cortical thickness. Moreover, for participants with MCI, gray matter NDI—but not cortical thickness—was lower in temporal, parietal, and posterior cingulate regions. Taken together, our results highlight the utility of NODDI metrics in detecting cortical microstructural degeneration that occurs prior to measurable macrostructural changes and overt clinical dementia.

scholarly journals Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jurre den Haan ◽  
Lajos Csinscik ◽  
Tom Parker ◽  
Ross W. Paterson ◽  
Catherine F. Slattery ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Retinal Thickness ◽  
Cortical Atrophy ◽  
Posterior Cortical Atrophy ◽  
Potential Biomarker
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