Inverse association for diagnosis of Alzheimer's disease subsequent to both melanoma and non‐melanoma skin cancers in a large, urban, single‐centre, Midwestern <scp>US</scp> patient population

Ibler, Erin; Tran, Gary; Orrell, Kelsey A.; Serrano, Linda; Majewski, S; Sable, Kimberly A.; Thiede, Rebecca; Laumann, Anne E.; West, Dennis P.; Nardone, Beatrice

doi:10.1111/jdv.14952

Cited by 15 publications

(15 citation statements)

References 11 publications

(38 reference statements)

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“…Our analysis of the risk of AD death in cancer patients relative to reference populations, stratified by race, cancer sites, age at diagnosis and time since cancer diagnosis, suggests a decreased risk of AD death in white patients diagnosed with different solid tumors or leukemias at the age of ≥45 years. This agrees with previous studies which reported inverse associations between cancer and the risk of AD [53][54][55][56]. However, our work identified specific solid tumors and hematolymphopoietic malignancies associated with a decreased risk of AD death in white patients and demonstrated modification of this protective effect by both age at diagnosis and time since cancer diagnosis.…”

Section: Discussionsupporting

confidence: 93%

“…Across several cancer types, our results for white patients are consistent with the results reported by a national veterans cohort study [39], with notable exceptions of melanoma and prostate cancer, for which the veterans study found increased risk of AD, while our results suggest decreased risk of AD death for melanoma and no difference in the risk of AD death for prostate cancer patients. However, our results for melanoma are supported by a large single-center US population study, which also found an inverse association between melanoma and the risk of AD [53]. The difference between the results of our study and those from the national veterans study for prostate cancer may stem from a possible difference between the prostate cancer cohorts in the use of androgen-deprivation therapy (ADT), which was found by some but not all investigators to increase the risk of AD [54].…”

Section: Interpretations Of the Cancer-ad Association Datasupporting

confidence: 83%

“…Importantly, the effect of cancer chemotherapy and/or radiation therapy does not seem to be fully responsible for the decreased risk of AD in cancer patients, because the lower incidence of AD was also reported for non-melanoma skin cancers, which are rarely, if ever, treated with radiotherapy and/or cytotoxic cancer chemotherapy [53].…”

Section: Effects Of Radiotherapymentioning

confidence: 99%

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Risk of Alzheimer’s Disease in Cancer Patients: Analysis of Mortality Data from the US SEER Population-Based Registries

Mezencev

Chernoff

2020

Cancers

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Previous studies have reported an inverse association between cancer and Alzheimer’s disease (AD), which are leading causes of human morbidity and mortality. We analyzed the SEER (Surveillance, Epidemiology, and End Results) data to estimate the risk of AD death in (i) cancer patients relative to reference populations stratified on demographic and clinical variables, and (ii) female breast cancer (BC) patients treated with chemotherapy or radiotherapy, relative to those with no/unknown treatment status. Our results demonstrate the impact of race, cancer type, age and time since cancer diagnosis on the risk of AD death in cancer patients. While the risk of AD death was decreased in white patients diagnosed with various cancers at 45 or more years of age, it was increased in black patients diagnosed with cancers before 45 years of age (likely due to early onset AD). Chemotherapy decreased the risk of AD death in white women diagnosed with BC at the age of 65 or more, however radiotherapy displayed a more complex pattern with early decrease and late increase in the risk of AD death during a prolonged time interval after the treatment. Our data point to links between molecular mechanisms involved in cancer and AD, and to the potential applicability of some anti-cancer treatments against AD.

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Section: Discussionsupporting

confidence: 93%

Section: Interpretations Of the Cancer-ad Association Datasupporting

confidence: 83%

Section: Effects Of Radiotherapymentioning

confidence: 99%

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Risk of Alzheimer’s Disease in Cancer Patients: Analysis of Mortality Data from the US SEER Population-Based Registries

Mezencev

Chernoff

2020

Cancers

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“…One way that Netrin-1 may protect against Alzheimer’s is by negatively regulating amyloid peptide [ 46 ]. Since Alzheimer’s patients appear to have reduced melanoma incidence [ 47 ], the low Netrin-1 expression and high amyloid beta levels produced in Alzheimer’s brains could represent a possible protective factor against melanoma. In contrast, the relatively higher levels of Netrin-1 in brains of non-Alzheimer’s patients could facilitate the formation of metastatic melanoma lesions by attracting, as suggested by our data, Neogenin-receptor-expressing aggressive melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells

Untiveros

Raskind

Linares

et al. 2022

IJMS

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Netrin-1 is a neural guidance factor that regulates migration and positioning of neural crest-derived cells during embryonic development. Depending on the type of Netrin-1 receptor expression, cells are either attracted or repulsed by Netrin-1. Postnatal expression of Netrin-1 is detected in brain, colon, liver, and kidney, which are common sites of cancer metastasis, including melanoma. Thus, understanding the dynamics between Netrin-1 and its receptors could explain the attraction of melanoma towards these Netrin-1-expressing tissues. Here, we investigate whether the Netrin-1-attractive receptor Neogenin can affect migration of melanoma cells towards a Netrin-1 source. Results from Western blot (WB) analysis show higher expression of Neogenin in aggressive compared to non-aggressive melanoma cells. Cell migration experiments show increased migration of Neogenin-expressing aggressive melanoma cells towards exogenous, soluble recombinant human Netrin-1 and towards a Netrin-1-expressing cell line. Furthermore, WB reveals ERK1/2 activation and increased N-cadherin expression in Neogenin-expressing aggressive melanoma cells treated with rhNetrin-1. Moreover, treatment with anti-Neogenin blocking antibody caused decreased migration towards Netrin-1-expressing cells and reduced ERK1/2 activity in Neogenin-expressing aggressive melanoma cells. These results suggest Neogenin may play a role during migration of melanoma cells towards Netrin-1 via ERK1/2 signaling.

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“…A significantly decreased risk of subsequent Alzheimer’s disease in both malignant melanoma patients and NMSC patients was also observed. 90 …”

Section: Alzheimer’s Disease and Skin Cancermentioning

confidence: 99%

The Relationship Between Alzheimer’s Disease and Skin Diseases: A Review

Zhang¹,

Zhang²,

Tang³

et al. 2021

CCID

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Alzheimer’s disease is the most common type of dementia placing a heavy burden on the healthcare system worldwide. Skin diseases are also one of the most common health problems. Several skin diseases are associated with Alzheimer’s disease through different mechanisms. This review summarizes the relationship between Alzheimer’s disease and several types of skin diseases, including bullous pemphigoid, hidradenitis suppurativa, psoriasis, skin cancer, and cutaneous amyloidosis, and provides suggestions based on these associations. Neurologists, dermatologists, and general practitioners should be aware of the relationship between Alzheimer’s disease and skin diseases. Dermatology/neurology consultation or referral is necessary when needed.

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Inverse association for diagnosis of Alzheimer's disease subsequent to both melanoma and non‐melanoma skin cancers in a large, urban, single‐centre, Midwestern US patient population

Abstract: These findings add to the growing body of evidence for a decreased risk of AD in patients with various cancers and highlight the need for ongoing research to elucidate both neurologic and biologic mechanisms that may underlie this apparent inverse association.

Cited by 15 publications

References 11 publications

Risk of Alzheimer’s Disease in Cancer Patients: Analysis of Mortality Data from the US SEER Population-Based Registries

Risk of Alzheimer’s Disease in Cancer Patients: Analysis of Mortality Data from the US SEER Population-Based Registries

Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells

The Relationship Between Alzheimer’s Disease and Skin Diseases: A Review

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