Rapid β-Amyloid Deposition and Cognitive Impairment After Cholinergic Denervation in APP/PS1 Mice

The spatial-temporal relationships between gray and white matter (WM) degeneration during preclinical and early symptomatic Alzheimer's disease are poorly understood. We characterized β-amyloid deposition, cortical volume and WM degeneration in 44 subjects including healthy control (N=23), amnestic mild cognitive impairment (aMCI) (N=19), and early Alzheimer's subjects (N=2). Integrated PET-MRI provided simultaneous measurement of 18F-Florbetapir uptake in cortical areas, regional brain volumes from structural MRI, and WM tract integrity metrics from diffusion MRI using biophysical modeling. Across the cohort of healthy control and aMCIs, cortical volumes correlated poorly with β-amyloid deposition in the same area (p < 0.05 only in the posterior cingulate and parietal lobe). WM degeneration correlated significantly with both amyloid and volume of connected cortical areas, but more strongly with volume. Diffusion MRI metrics for WM demyelination and/or axonal loss could therefore provide new biomarkers associated with clinical Alzheimer's conversion. These WM changes may represent sequential propagation of Alzheimer's neurodegeneration between functionally connected regions, and/or evidence of direct WM injury during the Alzheimer's pathology cascade.

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Neuroprotective effect of 1-Deoxynojirimycin on cognitive impairment, β-amyloid deposition, and neuroinflammation in the SAMP8 mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.06.106 ◽

2018 ◽

Vol 106 ◽

pp. 92-97 ◽

Cited By ~ 10

Author(s):

Weike Chen ◽

Tingting Liang ◽

Wenwen Zuo ◽

Xin Wu ◽

Zibo Shen ◽

...

Keyword(s):

Cognitive Impairment ◽

Neuroprotective Effect ◽

Amyloid Deposition ◽

Β Amyloid ◽

Samp8 Mice

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Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

Current Alzheimer Research ◽

10.2174/1567205016666190827120108 ◽

2019 ◽

Vol 16 (9) ◽

pp. 834-835

Author(s):

Petter Järemo ◽

Alenka Jejcic ◽

Vesna Jelic ◽

Tasmin Shahnaz ◽

Homira Behbahani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cell Damage ◽

Control Group ◽

Red Cell ◽

Oxygen Release ◽

Regulatory Pathways ◽

Β Amyloid ◽

2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

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Biological Signatures of Alzheimer’s Disease

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200228095553 ◽

2020 ◽

Vol 20 (9) ◽

pp. 770-781 ◽

Cited By ~ 12

Author(s):

Poornima Sharma ◽

Anjali Sharma ◽

Faizana Fayaz ◽

Sharad Wakode ◽

Faheem H. Pottoo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Senile Plaque ◽

Senile Plaques ◽

Amyloid Deposition ◽

Immune Defense ◽

Amyloid Angiopathy ◽

Microvascular Changes ◽

Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

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Effect of Patient-Specific Preanalytic Variables on CSF Aβ1–42 Concentrations Measured on an Automated Chemiluminescent Platform

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa145 ◽

2020 ◽

Author(s):

Jacqueline A Darrow ◽

Amanda Calabro ◽

Sara Gannon ◽

Amanze Orusakwe ◽

Rianne Esquivel ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Patient Specific ◽

Csf Biomarkers ◽

Clinical Settings ◽

Blood Contamination ◽

Gradient Effect ◽

Β Amyloid ◽

The Impact ◽

Gradient Effects

Abstract Background Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF β-amyloid 1–42 (Aβ1–42) concentrations. Methods Aβ1–42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients). Results Patient fasting did not significantly affect CSF Aβ1–42 levels. While assessing gradient effects, Aβ1–42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aβ1–42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aβ1–42 concentrations. Conclusions The preanalytical variables examined here do not have significant effects on Aβ1–42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aβ1–42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aβ1–42 concentrations once specimens have been frozen.

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