Lack of association between mtDNA haplogroups and Alzheimer’s disease in Tuscany

Mancuso, Michelangelo; Nardini, Marco; Micheli, D; Rocchi, Anna; Nesti, Claudia; Giglioli, Nj; Petrozzi, Lucia; Rossi, C. A.; Ceravolo, Roberto; Bacci, Andrea; Choub, Anna; Ricci, Giulia; Tognoni, Gloria; Manca, Maria Laura; Siciliano, Gabriele; Murri, Luigi

doi:10.1007/s10072-007-0807-z

Cited by 41 publications

(34 citation statements)

References 18 publications

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“…ApoE4 allele was confirmed as a risk factor for AD, but no association between ApoE alleles and mtDNA haplogroups was observed [93]. Our data also excluded any association between mtDNA haplogroups, age of onset and mean survival [93].…”

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 52%

“…Further, there was no significant difference between genders as far as mtDNA haplogroups distribution in both AD patients and control groups [93]. ApoE4 allele was confirmed as a risk factor for AD, but no association between ApoE alleles and mtDNA haplogroups was observed [93]. Our data also excluded any association between mtDNA haplogroups, age of onset and mean survival [93].…”

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 53%

“…We studied the frequency of the European mtDNA haplogroups in a clinically well defined group of 209 unrelated patients and 191 controls with clear Tuscan origin (in order to minimize the risk of false associations between gene markers and disease). The frequency of haplogroups H, I, J, K, T, U, V, W, and X was not significantly different between AD and control groups [93]. Further, there was no significant difference between genders as far as mtDNA haplogroups distribution in both AD patients and control groups [93].…”

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 83%

“…The frequency of haplogroups H, I, J, K, T, U, V, W, and X was not significantly different between AD and control groups [93]. Further, there was no significant difference between genders as far as mtDNA haplogroups distribution in both AD patients and control groups [93]. ApoE4 allele was confirmed as a risk factor for AD, but no association between ApoE alleles and mtDNA haplogroups was observed [93].…”

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 83%

“…In our laboratory we did not find any evidence for an etiological role of haplogroup-associated polymorphisms [93]. We studied the frequency of the European mtDNA haplogroups in a clinically well defined group of 209 unrelated patients and 191 controls with clear Tuscan origin (in order to minimize the risk of false associations between gene markers and disease).…”

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 97%

See 4 more Smart Citations

Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?

Mancuso

Orsucci²,

Siciliano³

et al. 2008

CAR

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To date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Abeta, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question "what comes first".

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Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 52%

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 53%

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 83%

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 83%

Section: Mitochondrial Haplogroups Are Involved In Alzheimer's Disease?mentioning

confidence: 97%

See 3 more Smart Citations

Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?

Mancuso

Orsucci²,

Siciliano³

et al. 2008

CAR

View full text Add to dashboard Cite

show abstract

No evidence of association between common European mitochondrial DNA variants in Alzheimer, Parkinson, and migraine in the Spanish population

Fachal

Mosquera-Miguel

Pástor

et al. 2014

American J of Med Genetics Pt B

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Certain mitochondrial DNA (mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases.

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Exploratory analysis of mtDNA haplogroups in two Alzheimer's longitudinal cohorts

Swerdlow

Hui

Chalise

et al. 2020

Alzheimer's & Dementia

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Introduction Inherited mitochondrial DNA (mtDNA) variants may influence Alzheimer's disease (AD) risk. Methods We sequenced mtDNA from 146 AD and 265 cognitively normal (CN) subjects from the University of Kansas AD Center (KUADC) and assigned haplogroups. We further considered 244 AD and 242 CN AD Neuroimaging Initiative (ADNI) subjects with equivalent data. Results Without applying multiple comparisons corrections, KUADC haplogroup J AD and CN frequencies were 16.4% versus 7.6% (P = .007), and haplogroup K AD and CN frequencies were 4.8% versus 10.2% (P = .063). ADNI haplogroup J AD and CN frequencies were 10.7% versus 7.0% (P = .20), and haplogroup K frequencies were 4.9% versus 8.7% (P = .11). For the combined 390 AD and 507 CN cases haplogroup J frequencies were 12.8% versus 7.3% (P = .006), odds ratio (OR) = 1.87, and haplogroup K frequencies were 4.9% versus 9.5% (P = .010), OR = 0.49. Associations remained significant after adjusting for apolipoprotein E, age, and sex. Conclusion This exploratory analysis suggests inherited mtDNA variants influence AD risk.

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Lack of association between mtDNA haplogroups and Alzheimer’s disease in Tuscany

Cited by 41 publications

References 18 publications

Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?

Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?

No evidence of association between common European mitochondrial DNA variants in Alzheimer, Parkinson, and migraine in the Spanish population

Exploratory analysis of mtDNA haplogroups in two Alzheimer's longitudinal cohorts

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