Ellingtongentry3816

Urokinase-type plasminogen activator (uPA) is a serine proteinase found in excitatory synapses located in the II/III and V cortical layers. The synaptic release of uPA promotes the formation of synaptic contacts and the repair of synapses damaged by various forms of injury, and its abundance is decreased in the synapse of Alzheimer's disease (AD) patients. Inactivation of the Wingless/Int1 (Wnt)-β-catenin pathway plays a central role in the pathogenesis of AD. Soluble amyloid-β (Aβ) prevents the phosphorylation of the low-density lipoprotein receptor-related protein-6 (LRP6), and the resultant inactivation of the Wnt-β-catenin pathway prompts the amyloidogenic processing of the amyloid-β protein precursor (AβPP) and causes synaptic loss.

To study the role of neuronal uPA in the pathogenesis of AD.

We used in vitro cultures of murine cerebral cortical neurons, a murine neuroblastoma cell line transfected with the APP-695 Swedish mutation (N2asw), and mice deficient on either plasminogen, or uPA, or its receptor (uPAR).

We show that uPA activates the Wnt-β-catenin pathway in cerebral cortical neurons by triggering the phosphorylation of LRP6 via a plasmin-independent mechanism that does not require binding of Wnt ligands (Wnts). Our data indicate that uPA-induced activation of the Wnt-β-catenin pathway protects the synapse from the harmful effects of soluble Aβ and prevents the amyloidogenic processing of AβPP by inhibiting the expression of β-secretase 1 (BACE1) and the ensuing generation of Aβ40 and Aβ42 peptides.

uPA protects the synapse and antagonizes the inhibitory effect of soluble Aβ on the Wnt-β-catenin pathway by providing an alternative pathway for LRP6 phosphorylation and β-catenin stabilization.

uPA protects the synapse and antagonizes the inhibitory effect of soluble Aβ on the Wnt-β-catenin pathway by providing an alternative pathway for LRP6 phosphorylation and β-catenin stabilization.

Mitochondrial DNA (mtDNA) may play a role in Alzheimer's disease (AD) and cognitive decline. A particular haplogroup of mtDNA, haplogroup J, has been observed more commonly in patients with AD than in cognitively normal controls.

We used two mtDNA haplogroups, H and J, to predict change in cognitive performance over five years. We hypothesized that haplogroup J carriers would show less cognitive resilience.

We analyzed data from 140 cognitively normal older adults who participated in the University of Kansas Alzheimer's Disease Research Center clinical cohort between 2011 and 2020. We used factor analysis to create three composite scores (verbal memory, attention, and executive function) from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change adjusting for age, sex, years of education, and APOE ɛ4 allele carrier status. Metabolism inhibitor We compared haplogroup H, the most common group, to haplogroup J, the potential risk group.

Haplogroup J carriers had significantly lower baseline performance and slower rates of improvement on tests of verbal memory compared to haplogroup H carriers. We did not observe differences in executive function or attention.

Our results reinforce the role of mtDNA in changes to cognitive function in a domain associated with risk for dementia, verbal memory, but not with other cognitive domains. Future research should investigate the distinct mechanisms by which mtDNA might affect performance on verbal memory as compared to other cognitive domains across haplogroups.

Our results reinforce the role of mtDNA in changes to cognitive function in a domain associated with risk for dementia, verbal memory, but not with other cognitive domains. Future research should investigate the distinct mechanisms by which mtDNA might affect performance on verbal memory as compared to other cognitive domains across haplogroups.

Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke's Cognitive Examination (ACE-III).

We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures.

Predicted ACE-III scores were categorized into three groups those with Expected (between -1.5 and 1.5 standard deviation; SD); Worse (< -1.5 SD); and Better (>1.5 SD) scores. Differences in the independent variables were then tested between these three groups.

Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer's disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables.

The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective.

The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective.Prior to the usual clinical symptoms of dementia, there can be subtle changes in cognitive function that differ from the normal age-related cognitive decline, which has been termed mild cognitive impairment (MCI). The increase in the numbers of individuals with possible MCI presenting to health care professionals, notably, General Practitioners (GPs), is going to rise dramatically in the coming years. With ever increasing demands on GPs, it is therefore timely to provide information that can be accessed by health care professionals to assist them in making appropriate diagnoses and to provide the most relevant, evidence-based treatment options. We have provided a comprehensive list of recommendations that aim to address key aspects of MCI in primary care. Specifically, these relate to detection and diagnosis; sharing the diagnosis, monitoring, and follow up; practical interventions to potentially delay progression; and personalizing care-planning, engagement, and patient motivation for the long term.

More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD).

To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders.

99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders.

Analyses identified that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum and the right uncinate fasciculus. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum.

This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.

This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.

The number of people with a migration background and dementia is increasing in Europe. All patients with suspected dementia have the right to an appropriate cognitive assessment and correct diagnosis for optimal treatment and support. Rowland Universal Dementia Assessment Scale (RUDAS) cognitive screening instrument is less affected by language, culture, and educational background, and adapted for use in multicultural populations.

To compare the diagnostic accuracy of RUDAS-S to the Swedish version of Mini-Mental State Examination (MMSE-SR) for detecting dementia in a multicultural group of outpatients in Swedish memory clinics.

We tested 123 outpatients (36 nonnative Swedish), in 4 memory clinics in Southern Sweden with RUDAS-S to supplement the usual cognitive assessment.

RUDAS-S had moderate to good diagnostic performance for detecting dementia in a multicultural population in Sweden, with an area under the receiver operating characteristic curve (AUC) of 0.81. At a cutoff score <25 its sensitivity was 0.92, specificity 0.60, and accuracy 76%. The AUC for the MMSE-SR was 0.79. At a cutoff score <23 its sensitivity was 0.65, specificity 0.81, and accuracy 73%.

RUDAS-S is at least as accurate as MMSE-SR for detecting dementia in memory clinics in Sweden and can be used for all patients undergoing a cognitive assessment, irrespective of their cultural, language, and educational background. However, there is a need for other cross-cultural cognitive tests to complement RUDAS-S to extend cognitive examination.

RUDAS-S is at least as accurate as MMSE-SR for detecting dementia in memory clinics in Sweden and can be used for all patients undergoing a cognitive assessment, irrespective of their cultural, language, and educational background. However, there is a need for other cross-cultural cognitive tests to complement RUDAS-S to extend cognitive examination.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer's disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids.

The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.e., Aβ1-40, Aβ1-42, tau, and α-synuclein) levels in both red blood cells (RBCs) and plasma of CAA patients and HC, evaluating their role as putative peripheral biomarkers for CAA.

For this purpose, the proteins' concentration was quantified in RBCs and plasma by homemade immunoenzymatic assays in an exploratory cohort of 20 CAA patients and 20 HC.

The results highlighted a significant increase of Aβ1-40 and α-synuclein concentrations in both RBCs and plasma of CAA patients, while higher Aβ1-42 and t-tau levels were detected only in RBCs of CAA individuals compared to HC.