The H1 Haplotype of the Tau Gene (MAPT) is Associated with Mild Cognitive Impairment

Maria, Emilio Di; Cammarata, Sergio; Parodi, Maria Isola; Borghi, Roberta; Benussi, Luisa; Galli, M.L.; Galimberti, Daniela; Ghidoni, Roberta; Gonella, Davide; Novello, Cristina; Pollero, Valeria; Perroni, L; Odetti, Patrizio; Scarpini, Elio; Binetti, Giuliano; Tabaton, Massimo

doi:10.3233/jad-2010-1285

Cited by 20 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two haplotypes show different expression patterns of these genes, some of which have been implicated in neuro-degenerative disorders in late life, particularly among individuals with the H1 haplotype. 12 This region includes MAPT which encodes the tau protein, a major hallmark of various dementias, including Alzheimer’s disease and fronto-temporal dementia. 12–14 Mutations in MAPT have been consistently associated with fronto-temporal dementia, progressive supra-nuclear palsy and Parkinson’s disease.…”

Section: Main Textmentioning

confidence: 99%

Common variants at 6q22 and 17q21 are associated with intracranial volume

Ikram¹,

Fornage²,

Smith³

et al. 2012

Nat Genet

122

View full text Add to dashboard Cite

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study in 8,175 community-dwelling elderly did not reveal any genome-wide significant associations (p<5*10−8) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (p=3.4*10−11), a known height locus on chromosome 6q22, and rs9915547, tagging the inversion on chromosome 17q21 (p=1.5*10−12). We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 older persons (p=1.1*10−3 for 6q22 and p=1.2*10−3 for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age 14.5 months). Our data identify two loci associated with head size, with the inversion on 17q21 also likely involved in attaining maximal brain size.

show abstract

Section: Main Textmentioning

confidence: 99%

Common variants at 6q22 and 17q21 are associated with intracranial volume

Ikram¹,

Fornage²,

Smith³

et al. 2012

Nat Genet

122

View full text Add to dashboard Cite

show abstract

“…These results suggest 1] that the risk of MCI is influenced by tau protein gene variations and 2] that MCI shares a common genetic background with AD. The results may help elucidating the genetic risk to cognitive decline and designing effective clinical trials, future diagnostics and future therapies [63]. …”

Section: Tauopathiesmentioning

confidence: 99%

Tau pathology: predictive diagnostics, targeted preventive and personalized medicine and application of advanced research in medical practice

Gozes

2010

EPMA Journal

View full text Add to dashboard Cite

Microtubules are key cytoskeletal elements found in all eukaryotic cells. The microtubule shaft is composed of the heterodimer protein, tubulin and decorated with multiple microtubule associated protein, regulating microtubule function. Tau (tubulin associated unit) or MAPT (microtubule associated protein tau), among the first microtubule associated proteins to be identified, was implicated in microtubule initiation as well as assembly, with increased expression in neurons and specific association with axonal microtubules. Alzheimer’s disease (AD) is the most prevalent tauopathy, exhibiting tau-neurofibrillary tangles associated with cognitive dysfunction. AD is also characterized by β-amyloid plaques. An abundance of tau inclusions, in the absence of β-amyloid deposits, can be found in Pick’s disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases, collectively described as tauopathies. The increase in tau pathology in AD correlates with the associated cognitive decline. The current manuscript touches on the variability as well as common denominators of the various tau pathologies coupled to new approaches/current innovation in treatment of tauopathies in favor of advanced technologies in predictive diagnostics, targeted preventive and personalized medicine (PPPM).

show abstract

“…The tau deposited in the tangles in PSP brains is predominantly the 4R isoforms, which may indicate that exon 10 splicing is altered in these patients [37]. A genetic association with the tau H1 haplotype has also been reported to exist in the case of corticobasal degeneration (CBD) [38], Down syndrome [39], and even mild cognitive impairment (MCI) [40] or Parkinson's disease (PD) [41].…”

Section: Introductionmentioning

confidence: 95%

Recent Developments in Tau-Based Therapeutics for Neurodegenerative Diseases

Medina¹

2011

RPCN

View full text Add to dashboard Cite

Neurodegenerative diseases constitute a major public health issue due to an increasingly aged population as a consequence of generally improved medical care and demographic changes. Current drug treatment of Alzheimer's disease (AD), the most prevalent dementia, with cholinesterase inhibitors or NMDA antagonists has demonstrated very modest, symptomatic efficacy, leaving an unmet medical need for new, more effective therapies. Drug development efforts for AD in the last two decades have primarily focused on targets defined by the amyloid cascade hypothesis, so far with disappointing results. In contrast, tau-based strategies have received little attention until recently despite that the presence of extensive tau pathology is central to the disease. The discovery of mutations within the tau gene that cause fronto-temporal dementia demonstrated that tau dysfunction, in the absence of amyloid pathology, was sufficient to cause neuronal loss and clinical dementia. This review focuses on emerging therapeutic strategies aimed at treating the underlying causes of the tau pathology in tauopathies and AD, including some targets with significant potential in the field and which might be on the verge of providing new treatment paradigms within the coming years. Among those strategies, immunotherapy approaches will be mostly discussed. An update on 2010 patents regarding different aspects of tau-based therapeutic strategies is also provided.

show abstract

The H1 Haplotype of the Tau Gene (MAPT) is Associated with Mild Cognitive Impairment

Cited by 20 publications

References 0 publications

Common variants at 6q22 and 17q21 are associated with intracranial volume

Common variants at 6q22 and 17q21 are associated with intracranial volume

Tau pathology: predictive diagnostics, targeted preventive and personalized medicine and application of advanced research in medical practice

Recent Developments in Tau-Based Therapeutics for Neurodegenerative Diseases

Contact Info

Product

Resources

About