Altered phosphorylation patterns of some proteins can affect sporadic Alzheimer’s disease (sAD), according to the results of a post-mortem tissue analysis published in Brain Pathology.
The study researchers received post-mortem samples from the Institute of Neuropathology HUB-ICO-IDIBELL Biobank in Spain. Tissue processing occurred between 3 hours and 13 hours and 40 minutes after death. Researchers then assessed the samples through phosphoproteomic analysis, immunohistochemistry, and immunofluorescence.
Patients with AD (pathological cases; n = 15) were in the neurofibrillary tangle (NFT) Braak stage I to II (n = 5), III to IV (n = 5) and V to VI (n = 5). No neurological or psychiatric diseases were diagnosed in the controls (n = 9). All samples were taken from people between the ages of 33 and 92 years.
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In the entorhinal cortex, the study researchers observed that a total of 230 proteins and 214 phosphoproteins were dysregulated, in particular 57 and 65 in NFT stages I to II; 89 and 135 in stages III to IV; and 136 or 118 in stages V to VI. The patterns of hyper- or hypophosphorylation based on the NFT stage were not discernible.
There were between 10 and 40 common phosphoproteins in the NFT stages. The results showed no overlap between dysregulated proteins and phosphoproteins.
A genontological analysis of dysregulated proteins in the entorhinal cortex identified the relevant terms synapse organization, development of the nervous system, chemical synaptic transmission, neural systems, regulation of membrane potential, synaptic vesicle cycle, regulation of vesicle-mediated transport and dendritic development. among other.
In the frontal cortex, a total of 82 proteins and 167 phosphoproteins were dysregulated, especially 23 and 81 in NFT stages I to II; 31 and 92 in stages III to IV; and 37 and 79 in stages V to VI. The study researchers did not find any apparent patterns of hyper- or hypophosphorylation based on the NFT stage.
Across the NFT stages, there were 14 common phosphoproteins between stages V to VI and III to IV and 15 between III to IV and I to II. The results showed no overlap between dysregulated proteins and phosphoproteins.
A genontological analysis of dysregulated proteins in the frontal cortex identified, among other things, the relevant terms synapse organization, axon guidance, neurexins, neuroligins, chemical synaptic transmission, neuronal systems and dendrite development.
This study was limited by concomitant pathologies in the patients and the postmortem delay from death to tissue processing.
These results confirmed previous studies that identified altered protein phosphorylation in the entorhinal and frontal cortex in patients with advanced AD and provided “for the first time robust data on the first and intermediate stages of NFT pathology associated with AD”. It remains unclear what role protein dysregulation plays in normal aging, or sAD, and requires additional studies.
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Ferrer I, Andrés-Benito P, Ausín K, et al. Dysregulated Protein Phosphorylation: A Critical Condition on the Continuum of Brain Aging and Alzheimer’s Disease. Pathol of the brain. 2021; e12996. doi: 10.1111 / bpa.12996
