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P3‐118: Apoptosis and Autophagy Changes Correlate With Alzheimer's Disease Progression in Humans: A Stereological Postmortem Study
Author(s) -
Theofilas Panos,
Nguy Austin K.,
Thackrey Julia M.,
Ehrenberg Alexander J.,
Dunlop Sara,
Mejia Maria B.,
Armas Cristina,
Alho Ana T.,
Suemoto Claudia K.,
Paraizo Leite Renata Elaine,
Rodriguez Roberta Diehl,
Seeley William W.,
Eloah de Lucena Ferretti-Rebustini Renata,
Farfel Jose M.,
Rueb Udo,
Jacob-Filho Wilson,
Nitrini Ricardo,
Pasquallucci Carlos Augusto,
Neuhaus John,
Heinsen Helmut,
Grinberg Lea T.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1776
Subject(s) - neurofibrillary tangle , tangle , programmed cell death , brainstem , autophagy , apoptosis , pathology , neuroscience , neurodegeneration , pathological , alzheimer's disease , disease , medicine , biology , senile plaques , biochemistry , mathematics , pure mathematics
in the limbic system and progressively spreads into primary processing and sensory regions such as the primary visual cortex and the retina. For the first time, here we assess the propagation of Ab42 peptide-mediated amyloidogenesis and pro-inflammatory gene expression (at the level of miRNA, mRNA and protein) in the neocortical-thalamic-retinal visual pathway of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum (sulfate). Methods:5xFAD Tg-AD murine models, RNA sequencing, GeneChip (microRNA and mRNA), RT-PCR, LED-Northern, Western, ELISA and bioinformatics analysis. Results:The three most significant findings were (i) in aluminum-supplemented animals, markers for inflammatory neuropathology appeared in both the brain and the retina as evidenced by an evolving presence of Ab42 peptides; (ii) increases in Ab42 peptide abundance in these animals were accompanied by the up-regulation of several pro-inflammatory markers including cyclooxygenase-2 (COX-2) and C-reactive protein (CRP); and (iii) that as similarly reported in other Tg-AD murine models, there was a significantly accelerated development of Ab42-mediated inflammatory neuropathology in 5xFAD Tg-AD mice fed aluminum. Conclusions: Taken together the results indicate that in the 5xFAD Tg-ADmodel aluminum not only enhances an Ab42-mediated inflammatory neurodegeneration in the brain but also significantly induces AD-type neuropathology in anatomically-linked primary sensory areas that involve the acquisition and processing of visual signals.