Spikes and diffusion waves in one-dimensional model of chemotaxis

We consider the one-dimensional initial value problem for the viscous transport equation with nonlocal velocity $u_t = u_{xx} - \left(u (K^\prime \ast u)\right)_{x}$ with a given kernel $K'\in L^1(\R)$. We show the existence of global-in-time nonnegative solutions and we study their large time asymptotics. Depending on $K'$, we obtain either linear diffusion waves ({\it i.e.}~the fundamental solution of the heat equation) or nonlinear diffusion waves (the fundamental solution of the viscous Burgers equation) in asymptotic expansions of solutions as $t\to\infty$. Moreover, for certain aggregation kernels, we show a concentration of solution on an initial time interval, which resemble a phenomenon of the spike creation, typical in chemotaxis models

Local and Global Well-Posedness for Aggregation Equations and Patlak-Keller-Segel Models with Degenerate Diffusion

Recently, there has been a wide interest in the study of aggregation equations and Patlak-Keller-Segel (PKS) models for chemotaxis with degenerate diffusion. The focus of this paper is the unification and generalization of the well-posedness theory of these models. We prove local well-posedness on bounded domains for dimensions $d\geq 2$ and in all of space for $d\geq 3$, the uniqueness being a result previously not known for PKS with degenerate diffusion. We generalize the notion of criticality for PKS and show that subcritical problems are globally well-posed. For a fairly general class of problems, we prove the existence of a critical mass which sharply divides the possibility of finite time blow up and global existence. Moreover, we compute the critical mass for fully general problems and show that solutions with smaller mass exists globally. For a class of supercritical problems we prove finite time blow up is possible for initial data of arbitrary mass.Comment: 31 page

Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease

Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluated longitudinally families affected by dominantly inherited Alzheimer disease (DIAD). Methods: Mutation carriers (n=310) and non-carriers (n=201) underwent neuroimaging, including gradient echo MR sequences to detect CMHs, neuropsychological, and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical marker of disease. Results: Three percent of non-carriers and eight percent of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMH. APOE-ε4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in clinical dementia rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of two or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95±10.04 per year). Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug related CMHs

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field