Associating infection by Chlamydia pneumoniae and the presence of amyloid-β plaques in the brains of Alzheimer’s disease/dementia patients

Sporadic late-onset AD (LOAD) is the most common form of dementia (Woods et al, 2020). In recent years, significant attention has been given to the role of infection in the pathogenesis of late-onset AD/dementia. The Cpn pathogen has been an organism of particular focus following the seminal study Balin et. al 1998 which found that Cpn DNA was present in 90% of brains from patients diagnosed with LOAD. Subsequent immunohistochemical studies demonstrated that Cpn antigens were present in the frontal and temporal cortices of LOAD brains and that Aβ amyloid plaques found in those regions of the brain co-localize with areas of Cpn immunoreactivity (Hammond et al 2010). This study aims to quantitate Chlamydia pneumoniae (Cpn) antigen(s) and Aβ amyloid plaques throughout the limbic system and cortical areas of brains from individuals diagnosed with late-onset Alzheimer’s disease (AD)/dementia and from individuals diagnosed with non-demented conditions. It was expected that the load of Cpn will positively correlate with the load of amyloid plaques in the brains investigated. Furthermore, as it is well established that amyloid plaques are a hallmark of Alzheimer’s disease pathology, it is assumed that the load of amyloid plaques and Cpn inclusions will be greater in the brains of individuals diagnosed with AD/dementia compared to the load of amyloid plaques and Cpn inclusions in brains from individuals not diagnosed with AD/dementia. Sections of the hippocampus and the prefrontal cortex were dissected and processed for immunostaining from the eight cadaver brains that had been donated to the Pennsylvania Human Gifts Registry. The brains selected included an equal number of 2 brains with confirmed dementia/AD and brains with no diagnosis of AD/dementia. AD/dementia or non-AD/dementia status was determined based on the listed cause of death (COD. Five sections from the hippocampus and the prefrontal cortex were immunolabeled with specific antibodies for amyloid plaques and Cpn and then digitally imaged at 40X. The Cpn inclusions and amyloid plaques were counted in each region and normalized using the equivalent total area/section. The data was recorded as mean counts per brain section. The AD/dementia brains showed a load of 1854.00±210.31 amyloid plaques and a load of 2272.75±395.72 Cpn inclusions in the hippocampus. The AD/dementia prefrontal cortex displayed a load of 3793.75±997.02 amyloid plaques and a load of 1833.25±470.02 Cpn inclusions The non-AD/dementia brains showed a load of 263.00±223.06 amyloid plaques and a load of 332.00±220.30 Cpn inclusions in the hippocampus. The non-AD/dementia prefrontal cortex displayed a load of 970.25±636.08 amyloid plaques and a load of 424.75±324.22 Cpn inclusions. This preliminary study yielded data of an association between amyloid pathology and infection by Cpn in both AD/demented and non-AD/dementia brains. It was revealed that the load of Cpn does correlate with the load of amyloid plaques in all brains where amyloid plaque pathology was present. Furthermore, the load of amyloid plaques and Cpn inclusions were substantially greater in brains with an AD/dementia diagnosis compared to brains without and AD/dementia diagnosis. These data help to support prior work demonstrating a relationship between infection and LOAD pathology. Furthermore, this study demonstrated that the Human Gifts registry is a viable and valuable resource of tissue for research purposes

An analysis of President Barack Obama's Global Health Initiative within the framework of a women-centered approach to the socialdeterminants of health

published_or_final_versionPublic HealthMasterMaster of Public Healt

Splice-site contribution in alternative splicing of PLP1 and DM20: molecular studies in oligodendrocytes.

Item does not contain fulltextMutations in the proteolipid protein 1 (PLP1) gene cause the X-linked dysmyelinating diseases Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia 2 (SPG2). We examined the severity of the following mutations that were suspected of affecting levels of PLP1 and DM20 RNA, the alternatively spliced products of PLP1: c.453G>A, c.453G>T, c.453G>C, c.453+2T>C, c.453+4A>G, c.347C>A, and c.453+28_+46del (the old nomenclature did not include the methionine codon: G450A, G450T, G450C, IVS3+2T>C, IVS3+4A>G, C344A, and IVS3+28-+46del). These mutations were evaluated by information theory-based analysis and compared with mRNA expression of the alternatively spliced products. The results are discussed relative to the clinical severity of disease. We conclude that the observed PLP1 and DM20 splicing patterns correlated well with predictions of information theory-based analysis, and that the relative strength of the PLP1 and DM20 donor splice sites plays an important role in PLP1 alternative splicing