Chang TH, Tai YH, Dai YX, Chang YT, Chen TJ, Chen MH.
Association between vitiligo and subsequent risk of dementia: A population-based cohort study.
J Dermatol. 2021 Jan;48(1):28-33. Epub 2020 Nov 12
PubMed.
It’s an interesting hypothesis, but more especially for Parkinson’s disease (PD) than AD. The pathogenesis of vitiligo encompasses both melanocyte vulnerability and autoimmunity by interferon-γ-producing, melanocyte-specific CD81 T cells, and melanized neurons in the substantia nigra are preferentially lost in PD.
There is a recent report of a novel PSEN1 nonsense mutation, chr14: 73673106 c.881G>A (p.W294*) in acute encephalopathy with retinitis pigmentosa (You et al., 2020). Nevertheless, there are a great many more patients with AD caused by PSEN1/2 missense mutations without vitiligo, retinal, or nigral depigmentation/loss reported. Melanosomes are a good model to study intracellular protein transport, and presenilins have a role, but it’s premature to associate vitiligo with AD or PD pathogenesis (Wang et al., 2006).
The Taiwanese study, drawn from a national database of 23 million, has marginally greater power than the Korean study, with 39 and 16 vitiligo cases with dementia respectively. Nevertheless, associations need replication, and the results in the first attempt from Korea are not supportive. While lack of replication is not evidence against, the findings will need positive replication.
I am not aware of vitiligo being noted as a clinical feature in either neurodegenerative disorder, nor of any synthesis from GWAS that’s suggestive of this etiology. It would be helpful to have more detailed clinical and pathologic data from the double-positive cases to further examine the potential relationship between these disorders.
References:
You C, Zeng W, Deng L, Lei Z, Gao X, Zhang VW, Wang Y.
Identification and Clinical Analysis of the First Nonsense Mutation in the PSEN1 Gene in a Family With Acute Encephalopathy and Retinitis Pigmentosa.
Front Neurol. 2020;11:319. Epub 2020 May 5
PubMed.
Wang R, Tang P, Wang P, Boissy RE, Zheng H.
Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation.
Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):353-8.
PubMed.
Comments
University of Florida
It’s an interesting hypothesis, but more especially for Parkinson’s disease (PD) than AD. The pathogenesis of vitiligo encompasses both melanocyte vulnerability and autoimmunity by interferon-γ-producing, melanocyte-specific CD81 T cells, and melanized neurons in the substantia nigra are preferentially lost in PD.
There is a recent report of a novel PSEN1 nonsense mutation, chr14: 73673106 c.881G>A (p.W294*) in acute encephalopathy with retinitis pigmentosa (You et al., 2020). Nevertheless, there are a great many more patients with AD caused by PSEN1/2 missense mutations without vitiligo, retinal, or nigral depigmentation/loss reported. Melanosomes are a good model to study intracellular protein transport, and presenilins have a role, but it’s premature to associate vitiligo with AD or PD pathogenesis (Wang et al., 2006).
The Taiwanese study, drawn from a national database of 23 million, has marginally greater power than the Korean study, with 39 and 16 vitiligo cases with dementia respectively. Nevertheless, associations need replication, and the results in the first attempt from Korea are not supportive. While lack of replication is not evidence against, the findings will need positive replication.
I am not aware of vitiligo being noted as a clinical feature in either neurodegenerative disorder, nor of any synthesis from GWAS that’s suggestive of this etiology. It would be helpful to have more detailed clinical and pathologic data from the double-positive cases to further examine the potential relationship between these disorders.
References:
You C, Zeng W, Deng L, Lei Z, Gao X, Zhang VW, Wang Y. Identification and Clinical Analysis of the First Nonsense Mutation in the PSEN1 Gene in a Family With Acute Encephalopathy and Retinitis Pigmentosa. Front Neurol. 2020;11:319. Epub 2020 May 5 PubMed.
Wang R, Tang P, Wang P, Boissy RE, Zheng H. Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation. Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):353-8. PubMed.
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