Correlation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer's Disease.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer's disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, both of which are brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s, and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, positron emission tomography (PET) imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified the densities of two synaptic proteins, the presynaptic protein Synaptosome Associated Protein 25 (SNAP25) and the postsynaptic protein postsynaptic density protein 95 (PSD95) in the human brain, using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate gyrus, hippocampus, frontal, primary visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI), and subjects with dementia that have different levels of Alzheimer's pathology. SNAP25 is significantly reduced in ADD when compared to controls in the frontal cortex, visual cortex, and cingulate, while the hippocampus showed a smaller, non-significant reduction, and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to controls without dementia, although in the hippocampus, this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques, and Mini Mental State Examination (MMSE) scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. The differences were less marked in the entorhinal cortex and the hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Global Community Health Screening and Educational Intervention for Early Detection of Cardiometabolic Renal Disease.

The global burden of cardiometabolic renal disease is increasing, particularly in underserved communities. Twinepidemic Inc.'s Galvanize Healthy Living program conducts community screenings, risk assessments, and educational interventions globally. We screened 1209 subjects for cardiovascular-kidney-metabolic syndrome, assessing their disease knowledge and self-confidence. Mean age was 50, with 65% females and 35% males. Imaging post-risk assessment revealed abnormalities: EKG (16%), echocardiogram (10%), carotid plaque (9%), ABI (2.5%), and eye exam (3.6%, including 8 retinopathies, 14 cataracts). New onset DM was found in 8%, prediabetes in 18.5%, High LDL in 4.2%, low HDL in 40.2%, high triglycerides in 13.1%, and abnormal BP in 38%. In addition, 18.2% were reclassified to a higher category of risk levels after imaging. Significant improvements in knowledge and self-empowerment (all p < 0.001) were seen after educational interventions. This study underscores early risk assessment's potential to enhance health outcomes globally for underserved populations, validating POC imaging and emphasizing the role of accessible care and education in patient engagement and empowerment.