Impact of β-Amyloid on the Tau Pathology in Tau Transgenic Mouse and Tissue Culture Models

2006 ◽  
pp. 198-215
Author(s):  
Jürgen Götz ◽  
Della C. David ◽  
Lars M. Ittner
Keyword(s):  
Tissue Culture ◽  
Transgenic Mouse ◽  
Tau Pathology ◽  
Culture Models ◽  
Β Amyloid

scholarly journals O4-01-03: Dissecting tau-mediated toxicity in novel Tau transgenic mouse and tissue culture models

2008 ◽  
Vol 4 ◽  
pp. T184-T184
Author(s):  
Jurgen Gotz ◽  
Nicole Schonrock ◽  
Andreas Wiesner ◽  
Yazi Ke ◽  
Laita Bokhari ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Transgenic Mouse ◽  
Culture Models

scholarly journals Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Brain ◽  
2021 ◽  
Author(s):  
David Berron ◽  
Jacob W Vogel ◽  
Philip S Insel ◽  
Joana B Pereira ◽  
Long Xie ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Entorhinal Cortex ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Memory Impairment ◽  
Memory Performance ◽  
Hippocampal Atrophy ◽  
Tau Pathology ◽  
Β Amyloid ◽  
With Memory

Abstract In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.

scholarly journals A cortical immune network map identifies distinct microglial transcriptional programs associated with β-amyloid and Tau pathologies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ellis Patrick ◽  
Marta Olah ◽  
Mariko Taga ◽  
Hans-Ulrich Klein ◽  
Jishu Xu ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Frontal Cortex ◽  
Brain Aging ◽  
Immune Network ◽  
Tau Pathology ◽  
Cellular Mechanisms ◽  
Activated Microglia ◽  
Human Frontal Cortex ◽  
Β Amyloid ◽  
The Many

AbstractMicroglial dysfunction has been proposed as one of the many cellular mechanisms that can contribute to the development of Alzheimer’s disease (AD). Here, using a transcriptional network map of the human frontal cortex, we identify five modules of co-expressed genes related to microglia and assess their role in the neuropathologic features of AD in 540 subjects from two cohort studies of brain aging. Two of these transcriptional programs—modules 113 and 114—relate to the accumulation of β-amyloid, while module 5 relates to tau pathology. We replicate these associations in brain epigenomic data and in two independent datasets. In terms of tau, we propose that module 5, a marker of activated microglia, may lead to tau accumulation and subsequent cognitive decline. We validate our model further by showing that three representative module 5 genes (ACADVL, TRABD, and VASP) encode proteins that are upregulated in activated microglia in AD.

scholarly journals Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

Neurology ◽  
2017 ◽  
Vol 90 (1) ◽  
pp. e73-e81 ◽  
Author(s):  
Katarina Nägga ◽  
Anna-Märta Gustavsson ◽  
Erik Stomrud ◽  
Daniel Lindqvist ◽  
Danielle van Westen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Healthy Population ◽  
Lipid Levels ◽  
Tau Pathology ◽  
Lipoprotein Subfractions ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Β Amyloid

ObjectiveTo evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.MethodsThis is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.ResultsCSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.ConclusionsIncreased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

scholarly journals Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

2021 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

Tissue Culture Models

2009 ◽  
pp. 159-182
Author(s):  
Roger A. Vertrees ◽  
Jeffrey M. Jordan ◽  
Travis Solley ◽  
Thomas J. Goodwin
Keyword(s):  
Tissue Culture ◽  
Culture Models

Experimental Keloid Scar Models: A Review of Methodological Issues

2002 ◽  
Vol 6 (4) ◽  
pp. 354-359 ◽  
Author(s):  
M. P. Hillmer ◽  
S. M. MacLeod
Keyword(s):  
Tissue Culture ◽  
Experimental Models ◽  
Critical Importance ◽  
Methodological Issues ◽  
Keloid Scar ◽  
Keloid Scars ◽  
Culture Models ◽  
Keloid Formation ◽  
New Treatments ◽  
Early Benefit

Background: Keloid scars are benign fibrous proliferations in the dermis that arise after dermal trauma. The scars are raised in appearance and extend beyond the boundaries of the original wound. Scarring in predisposed individuals is out of proportion to the severity of the inciting wound. Current treatments sometimes yield early benefit but scars often resume exuberant growth. The pathophysiology of keloid scars is still poorly understood. In order for new treatments to be developed, the mechanisms leading to the formation of keloid scars must be further elucidated. The search for improved experimental models is of critical importance because such models have an important role to play in both the study of keloid formation and in the development of new therapies. Objective: The objective of this article is to introduce the reader to the experimental models available for studying keloid scars and to outline the advantages and limitations of animal and tissue culture models. Conclusion: Both models may help to elucidate the pathways of keloid formation and promote development and testing of therapies. Tissue culture is better suited to studies of pathogenesis, whereas the animal models are more suitable for therapeutic testing.

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