Cellular and molecular mechanisms of Dementia: Decoding the causal link of Diabetes Mellitus in Alzheimer’s disease

: Dementia and diabetes are the two major disorders that are linked at both biochemical and molecular levels which is due to the existing similarities between pancreatic beta-cells and neuronal cells at the transcription and translational levels. Both diseases have similar causative genes or factors and dementia is one of the advanced complications in about 50-52% of patients with type 2 diabetes mellitus (T2DM). Further, patients with T2DM are at a higher risk of neuronal degeneration and Alzheimer’s disease (AD). Dementia, which is most common in AD, is associated with diminished insulin receptors by nearly 80%. The impairment in insulin signaling thus leads to the development of dementia and AD. Biochemical changes in ‘tau’ protein and amyloid-beta proteins, make them critical players in the formation of plaques in patients with dementia and AD. Here, we decode various cellular and molecular mechanisms associated with the development of dementia in patients with diabetes and AD.

Dielectrophoresis of Amyloid-Beta Proteins as a Microfluidic Template for Alzheimer’s Research

We employed dielectrophoresis to a yeast cell suspension containing amyloid-beta proteins (Aβ) in a microfluidic environment. The Aβ was separated from the cells and characterized using the gradual dissolution of Aβ as a function of the applied dielectrophoretic parameters. We established the gradual dissolution of Aβ under specific dielectrophoretic parameters. Further, Aβ in the fibril form at the tip of the electrode dissolved at high frequency. This was perhaps due to the conductivity of the suspending medium changing according to the frequency, which resulted in a higher temperature at the tips of the electrodes, and consequently in the breakdown of the hydrogen bonds. However, those shaped as spheroidal monomers experienced a delay in the Aβ fibril transformation process. Yeast cells exposed to relatively low temperatures at the base of the electrode did not experience a positive or negative change in viability. The DEP microfluidic platform incorporating the integrated microtip electrode array was able to selectively manipulate the yeast cells and dissolve the Aβ to a controlled extent. We demonstrate suitable dielectrophoretic parameters to induce such manipulation, which is highly relevant for Aβ-related colloidal microfluidic research and could be applied to Alzheimer’s research in the future.

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer’s Disease?

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

Alzheimer’s Dementia From a Bilingual/Bicultural Perspective

Alzheimer’s dementia (AD) is a progressive, degenerative disease that occurs in the cerebral cortex due to increased levels of glutamate, the proliferation of plaque-forming amyloid beta proteins, and reactive gliosis. Establishing behavioral indicators of the disease (e.g., impairments of episodic memory) and use of neuroimaging technology that can substantiate medial temporal lobe brain structure deficiencies demonstrates an important clinical neuroanatomic relationship needed for early evaluation of possible AD diagnosis. This bilingual/bicultural case study details the cognitive and language impairments associated with AD over the course of 1 year. Utilization of a bilingual/bicultural case study may elucidate the pattern of language and cognitive decline in this understudied population. Formal and informal measures, observations, and magnetic resonance imaging (MRI) results are provided. Insights into cultural and linguistic differences are presented.