Alzheimer’s Disease and Cancer: When Two Monsters Cannot Be Together

Abstract

Alzheimer’s disease (AD) and cancer are among the leading causes of human death around the world. While neurodegeneration is the main feature of AD, the most important characteristic of malignant tumors is cell proliferation, placing these two diseases in opposite sides of cell division spectrum. Interestingly, AD and cancer’s pathologies consist of a remarkable common feature and that is the presence of active cell cycle in both conditions. In an in vitro model of primary adult neuronal culture, we previously showed that treating cell with beta amyloid forced neurons to start a cell cycle. Instead of cell division, however, neuronal cell cycle was aborted and a massive neurodegeneration was left behind as the consequence. A high level of cell cycle entry, which is a requirement for cancer pathogenesis, was reported in clinically diagnosed cases of AD, leading to neurodegeneration. The diverse clinical manifestation of a similar etiology, have puzzled researchers for many years. In fact, the evidence showed an inverse association between AD and cancer prevalence, suggesting that switching pathogenesis toward AD protects patients against cancer and vice versa. In this mini review, we discussed the possibility of involvement of cell proliferation and survival dysregulation as the underlying mechanism of neurodegeneration in AD, and the leading event to develop both disorders’ pathology. As examples, the role of phosphoinositide 3 kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in cell cycle re-entry and blocking autophagy are discussed as potential common intracellular components between AD and cancer pathogenesis, with diverse clinical diagnosis.

Identification of functionally connected multi-omic biomarkers for Alzheimer’s Disease using modularity-constrained Lasso

“…In addition, we observe 254 many of the top enriched pathways are related to cancer, such as PI3K -Akt signaling 255 pathway, Prostate cancer and small lung cancer. This finding provide support to the 256 hypothesis of shared pathological mechanism between cancer and AD [50][51][52][53].…”

Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer’s Disease Progression

“…Old postmitotic neurons try to repair their DNA by entering the cell cycle as replicative cells do. Their vast nucleo-cytoskeleton complexity, however, does not allow them to immortalize like cancer cells, and they die in the attempt [54,54,63,103]. The biological rescue mechanism of neuronal suicide is the reorganization of the nucleo-cytoskeleton through the massive expression of the highly regulated Lamin A [44] and the building of toxic NFTs (Figure 7).…”

Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases

“…This is an interesting aspect when considering that glial cells have extremely aggressive oncogenic capabilities (as proven by the dramatically malignant nature of glioblastomas). Notably, despite the agreement on the existence of an inverse association between AD and neoplastic diseases (patients with AD have a low risk of developing cancer and vice-versa) [26], glioblastoma is an exception. Indeed a direct co-morbidity relationship has been shown between AD and glioblastoma [27,28].…”

“…The role of the PI3K/Akt/mTOR (phosphoinositide 3 kinase/Akt/ mammalian target of rapamycin) pathway in cell cycle promoting has been proposed as a common intracellular signal transductor between AD and neoplasms. In addition, it has been hypothesized that cell proliferation and survival dysregulation may favour neurodegeneration in AD [26]. The PI3K/Akt/mTOR axis has been proposed to be crucial also in regulating defence mechanisms in the innate immune system [39].…”