Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population

Kero, Mia; Paetau, Anders; Polvikoski, Tuomo; Tanskanen, Maarit; Sulkava, Raimo; Jansson, Lilja; Myllykangas, Liisa; Tienari, Pentti J.

doi:10.1016/j.neurobiolaging.2012.09.017

Cited by 69 publications

(51 citation statements)

References 9 publications

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“…This is in line with the absence of cerebral amyloidosis in A2T carriers even at advanced age (45) and with the protected status of heterozygous carriers of A2V (5). These effects of A2T and A2V mutations on peptide aggregation are striking; however, the interpretation of A␤ aggregation studies in the context of any clinical phenotypes should take into account other aspects of A␤ and APP biology.…”

Section: A2x ؉ Wt A␤40supporting

confidence: 71%

“…1) are known to increase A␤ generation. Other mutations in the C-terminal part of A␤ (amino acids [43][44][45][46] shift the initial ⑀-cut by ␥-secretase from amino acids 50 -51 to amino acids 49 -50 and increase the relative amount of long, more aggregation-prone A␤ fragments versus shorter peptides, without increasing the total amount of A␤ (7)(8)(9). Other mutations, e.g.…”

mentioning

confidence: 99%

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The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation

Benilova

Gallardo

Ungureanu

et al. 2014

Journal of Biological Chemistry

137

148

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Section: A2x ؉ Wt A␤40supporting

confidence: 71%

mentioning

confidence: 99%

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation

Benilova

Gallardo

Ungureanu

et al. 2014

Journal of Biological Chemistry

137

148

View full text Add to dashboard Cite

“…In addition, all familial forms of AD identified so far are caused by mutations in the amyloid precursor protein (APP) or in presenilin proteins resulting in increased brain A␤ accumulation and alteration of A␤ production (4,5), suggesting that A␤ plays an important role in the development of AD. Interestingly, a coding mutation found in the APP gene resulting in a reduction of A␤ production is protective against AD and cognitive decline in the elderly (6,7) further supporting the view that A␤ is a key culprit in the pathobiology of AD. A␤ is generated by the sequential proteolytic cleavage of APP by ␤-and ␥-secretase.…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 83%

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation

Paris

Ait‐Ghezala

Bachmeier

et al. 2014

Journal of Biological Chemistry

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Background: Spleen tyrosine kinase (Syk) mediates microglial activation and neurotoxicity elicited by Alzheimer A␤ peptides. Results: Syk regulates A␤ production via NFB-dependent mechanisms and Tau phosphorylation by controlling the activation of glycogen synthase 3␤. Conclusion: Inhibition of Syk can interrupt the neuroinflammation, pathological A␤ accumulation, and Tau hyperphosphorylation in AD. Significance: Syk represents a therapeutic target for the key pathological lesions that define AD.

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“…Another recent study has provided evidence that a lowfrequency variant of the coding mutation (A673T) in the APP gene protects against AD and cognitive decline in the elderly without AD [47,48]. The discovery of the protective effect of the A673T substitution against AD provides proof of the principle that reducing the b-cleavage of APP may protect against the disease, and supports the clinical usefulness of the current amyloid-directed therapeutic research efforts.…”

Section: The Genetics Of Admentioning

confidence: 85%

FDG PET and the genetics of dementia

Nacmias

Berti

Piaceri

et al. 2013

Clin Transl Imaging

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Dementias are the most common neurodegenerative diseases and they are increasingly becoming a major public health problem. The most common form of dementia, affecting over 20 million people worldwide, is Alzheimer's disease (AD). AD is a neurodegenerative disease of the central nervous system mainly found in older adults, with an incidence that increases with age. With the development of newer technologies, including genetic screening technologies and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined; indeed, these approaches are able to provide support not only in the clinical diagnosis of dementia, but also in its presymptomatic evaluation. Many researchers agree that early identification of AD, before abnormal accumulation of amyloid and tau proteins, could provide an opportunity to hinder the progression of the disease. [18 F]2-fluoro-2-deoxy-D-glucose (FDG) PET studies have shown that decreased glucose metabolism in AD precedes clinical diagnosis and that the degree of clinical disability in AD correlates closely with the magnitude of the reduction in brain glucose metabolism. Data on presymptomatic mutation carriers from families with known early-onset autosomal dominant AD (familial AD) show reductions in the cerebral metabolic rate of glucose (CMRglc), consistent with the expected AD PET pattern, in the absence of severe atrophy on MRI. These results suggest that PET CMRglc measures have the potential to serve as preclinical biomarkers of dementia, useful also for tracking disease progression. This review highlights the role of genetics and FDG PET in understanding the pathogenesis of dementia.

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Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population

Cited by 69 publications

References 9 publications

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation

FDG PET and the genetics of dementia

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