Altered DNA base excision repair profile in brain tissue and blood in Alzheimer’s disease

Lillenes, Meryl S.; Rábano, Alberto; Støen, Mari; Riaz, Tahira; Misaghian, Dorna; Møllersen, Linda; Esbensen, Ying; Günther, Clara‐Cecilie; Selnes, Per; Stenset, Vidar; Fladby, Tormod; Tønjum, Tone

doi:10.1186/s13041-016-0237-z

Cited by 40 publications

(30 citation statements)

References 69 publications

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“…Our previous studies show a down-regulation of APE1 and an up-regulation of OGG1 in the prodromal phases of AD in the Tg-ArcSwe AD mouse model at the age of 4 months [62]. In support, we found lower APE1 mRNA levels in the blood and in the entorhinal cortex of AD patients than in healthy controls [63]. The entorhinal cortex is one of the first regions to be affected in AD [64] and alterations observed here may represent late changes in the progression of AD.…”

Section: Base Excision Dna Repair Of Oxidative Damage Is Decreased In Adsupporting

confidence: 69%

The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease

Desler

Lillenes

Tønjum

et al. 2019

CMC

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The current molecular understanding of Alzheimer's disease (AD) has still not resulted in successful interventions. Mitochondrial dysfunction of the AD brain is currently emerging as a hallmark of this disease. One mitochondrial function often affected in AD is oxidative phosphorylation responsible for ATP production, but also for production of reactive oxygen species (ROS) and for the de novo synthesis of pyrimidines. This paper reviews the role of mitochondrial produced ROS and pyrimidines in the aetiology of AD and their proposed role in oxidative degeneration of macromolecules, synthesis of essential phospholipids and maintenance of mitochondrial viability in the AD brain.

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Section: Base Excision Dna Repair Of Oxidative Damage Is Decreased In Adsupporting

confidence: 69%

The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease

Desler

Lillenes

Tønjum

et al. 2019

CMC

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“…Levels of expression of various BER components were found to be greater in postmortem brain tissue than in blood cells from live patients with AD or MCI and controls (89). The data indicated that changes in expression of BER genes precede AD development and might be useful as predictive biomarkers.…”

Section: Dna Damage and Repair In Ad And Hsv1mentioning

confidence: 99%

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

Itzhaki

2017

FASEB j.

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Support for the concept that herpes simplex virus type 1 (HSV1), when present in the brains of apolipoprotein E-ε4 carriers, is a major risk for Alzheimer's disease (AD) is increasing steadily, with over 120 publications providing direct or indirect evidence relevant to the hypothesis. No articles have contested the concept, apart from 3 published 13-18 yr ago. This review describes very recent studies on the role of HSV1 but refers also to older studies that provide background for some lesser-known related topics not covered in other recent reviews; these include the relevance of herpes simplex encephalitis and of epilepsy to AD, the action of IFN, and the possible relevance of the different types of DNA damage to AD-in particular, those caused by HSV1-and mechanisms of repair of damage. New epidemiologic data supporting previous studies on mild cognitive impairment and progression to AD are reviewed, as are those examining the relationship between total infectious burden (additive seropositivity to various microbes) and cognition/AD. The latter indicates the involvement of HSV1 and cytomegalovirus (and the necessity of taking into account any marked differences in sensitivity of antibody detection). Recent studies that provide further support for the occurrence of repeated reactivation of latent HSV1 in the brain in AD pathogenesis are also discussed.-Itzhaki, R. F. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts.

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“…For instance, the polymorphism of R194W (arginine 194 to tryptophan 194) of XRCC1 does not appear to be a significant risk factor of AD [151,152]. While reagent limitations restrained the detection of APE1 in post-mortem brain by immunohistochemistry [153], the APE1 mRNA level is decreased in entorhinal cortex in AD brains compared to controls (Figure 4) [154]. It thus remains to be determined whether BER dysfunction in AD is resulted through a coordinated manner.…”

Section: Coordination Of Ber Defects In Admentioning

confidence: 99%

“…It thus remains to be determined whether BER dysfunction in AD is resulted through a coordinated manner. A recent report has systemically determined the expression of OGG1, APE1, PARP1, and POLβ in a cohort of 42 ADs and 9 controls using quantitative real-time PCR [154]. Consistent with the discussions in Section 4.2, PARP1 mRNA expression is increased in hippocampus and entorhinal cortex ( Figure 4) [154]; while APE1 mRNA is only reduced in entorhinal cortex, POLβ is significantly reduced in frontal cortex, hippocampus, and entorhinal cortex ( Figure 4) [154], suggesting a possibility for alterations in more than one factor to impair BER during AD pathogenesis.…”

Section: Coordination Of Ber Defects In Admentioning

confidence: 99%

Contributions of DNA Damage to Alzheimer’s Disease

Lin

Kapoor

et al. 2020

IJMS

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Alzheimer's disease (AD) is the most common type of neurodegenerative disease. Its typical pathology consists of extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles. Mutations in the APP, PSEN1, and PSEN2 genes increase Aβ production and aggregation, and thus cause early onset or familial AD. Even with this strong genetic evidence, recent studies support AD to result from complex etiological alterations. Among them, aging is the strongest risk factor for the vast majority of AD cases: Sporadic late onset AD (LOAD). Accumulation of DNA damage is a well-established aging factor. In this regard, a large amount of evidence reveals DNA damage as a critical pathological cause of AD. Clinically, DNA damage is accumulated in brains of AD patients. Genetically, defects in DNA damage repair resulted from mutations in the BRAC1 and other DNA damage repair genes occur in AD brain and facilitate the pathogenesis. Abnormalities in DNA damage repair can be used as diagnostic biomarkers for AD. In this review, we discuss the association, the causative potential, and the biomarker values of DNA damage in AD pathogenesis.Int. J. Mol. Sci. 2020, 21, 1666 2 of 26 amyloid (senile) plaques in AD brain [9][10][11]. Furthermore, CDK5 activities affect DNA damage response [12], supporting a linkage of DNA damage with AD [13,14].Aβ peptides are directly produced by sequential cleavages of APP by βand γ-secretase; the proteolytic c-terminal fragment of APP (CTFβ) of β-secretase is cleaved within the cell membrane by γ-secretase to generate neurotoxic Aβ peptides with length ranging from 38-43 residues [15][16][17][18][19]. The 40 residue Aβ peptide (Aβ 1-40 ) is the major product, accounting for more than 50% of Aβ peptides [9,17]. Although the Aβ 1-42 peptide consists of less than 10% of Aβ peptides [16,17], it is more neurotoxic and associates with a higher risk of AD because of its propensity of aggregation [9]. The importance of Aβ in AD pathogenesis is illustrated by mutations of APP, PSEN1, and PREN2 genes in familial AD with the latter two encoding the presenilin 1 and presenilin 2 subunit of γ-secretase. Individuals with these mutations develop early onset dementia in an autosomal-dominant manner [20]; the typical onset starts between 30 and 50 years of age in PSEN1 mutant carriers with some being affected at in their 20s [20,21]. γ-secretase with mutant presenilin 1 or presenilin 2 subunit favors Aβ 1-42 production [16,17]. These genetic observations led to formation of the amyloid cascade hypothesis, in which abnormal Aβ drives AD pathogenesis via regulating other pathological events including tau pathology [22][23][24][25][26][27]. This hypothesis is supported by the similar pathological features between familial AD and sporadic late onset AD (LOAD) [20]. Although familial AD constitutes less than 1% of AD cases [28,29], the hypothesis has been widely accepted to guide research in advancing the understanding of both familial AD and LOAD in the past two decades [30,31].Nonetheless, it is becoming in...

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Altered DNA base excision repair profile in brain tissue and blood in Alzheimer’s disease

Cited by 40 publications

References 69 publications

The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease

The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

Contributions of DNA Damage to Alzheimer’s Disease

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