Abstract
Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer’s disease (AD) and sporadic Parkinson’s disease (sPD). Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2, Pick’s disease (PiD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD-tau). The studies have disclosed variable gene regulation which is: (1) disease-dependent in the frontal cortex area 8 in AD, sPD, sCJD MM1 and VV2, PiD, PSP and FTLD-tau; (2) region-dependent as seen when comparing the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 (FC) in AD; the substantia nigra, putamen, FC, and angular gyrus in PD, as well as the FC and cerebellum in sCJD; (3) genotype-dependent as seen considering sCJD MM1 and VV2; and (4) stage-dependent as seen in AD at different stages of disease progression. These observations show that regulation of inflammation is much more complicated and diverse than currently understood, and that new therapeutic approaches must be designed in order to selectively act on specific targets in particular diseases and at different time points of disease progression.
Highlights
Alzheimer’s disease (AD), Parkinson’s disease (PD), Creutzfeldt-Jakob’s disease (CJD), and tauopathies are neurodegenerative diseases presenting most commonly in aged individuals, and characterized by the accumulation of abnormal protein aggregates in the neuropil, neurons, and, in some conditions, in glial cells, β-amyloid and hyper-phosphorylated 3R and 4R tau in AD, altered α-synuclein in PD, 3R or 4R hyper-phosphorylated tau in tauopathies, and pathogenic, mostly proteinase resistant, prion protein or prion in Creutzfeldt-Jakob disease (CJD)
The present review up-dates general aspects linked to neuroinflammation in AD, PD, CJD and tauopathies, and summarizes personal work published in the last two years dealing with gene expression profiles of cytokines and mediators of the immune response in a wide range of neurodegenerative diseases including AD, sporadic Parkinson’s disease (sPD), sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 at different stages of disease progression and in specific vulnerable regions
Variations in several genes putatively involved in inflammation and immune responses have been suggested as risk factors of late-onset Alzheimer’s disease (LOAD) on the basis of a genome-wide association study (GWAS) searching for single nucleotide polymorphisms associated with LOAD, data from the LOAD Consortium, and whole genome sequencing
Summary
Alzheimer’s disease (AD), Parkinson’s disease (PD), Creutzfeldt-Jakob’s disease (CJD), and tauopathies are neurodegenerative diseases presenting most commonly in aged individuals, and characterized by the accumulation of abnormal protein aggregates in the neuropil, neurons, and, in some conditions, in glial cells, β-amyloid and hyper-phosphorylated 3R and 4R tau in AD, altered α-synuclein in PD, 3R or 4R hyper-phosphorylated tau in tauopathies, and pathogenic, mostly proteinase resistant, prion protein or prion in CJD. The present review up-dates general aspects linked to neuroinflammation in AD, PD, CJD and tauopathies, and summarizes personal work published in the last two years dealing with gene expression profiles of cytokines and mediators of the immune response in a wide range of neurodegenerative diseases including AD, sPD, sCJD subtypes MM1 and VV2 at different stages of disease progression and in specific vulnerable regions. This is followed by a description of unpublished observations in the frontal cortex in tauopathies including Pick’s disease, progressive supranuclear palsy and frontotemporal lobar degeneration linked to the P301L mutation in MAPT. This last set of data was considered appropriate to includea here as it was obtained using the same methods and procedures as in studies noted in previous paragraphs, and it further documents disease specificities in the inflammatory response among neurodegenerative diseases with abnormal protein aggregates
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