&lt;i&gt;TAU&lt;/i&gt; Haplotype and the &lt;i&gt;Saitohin&lt;/i&gt; Q7R Gene Polymorphism Do Not Influence CSF Tau in Alzheimer’s Disease and Are Not Associated with Frontotemporal Dementia or Parkinson’s Disease

Johansson, Annica; Zetterberg, Henrik; Håkansson, Anna; Nissbrandt, Hans; Blennow, Kaj

doi:10.1159/000086428

Cited by 21 publications

(20 citation statements)

References 98 publications

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“…Association of the H1 haplotype at the MAPT locus with PSP and CBD has been described and replicated8; however, association studies of variants at MAPT in PD have produced conflicting results14,15. Our data provide unequivocal evidence for an association of the MAPT locus with PD.…”

supporting

confidence: 54%

Genome-wide association study reveals genetic risk underlying Parkinson's disease

et al. 2009

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We performed a genome-wide association study (GWAS) in 1,713 Caucasian patients with Parkinson’s disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, two strong association signals were observed: in the α-synuclein gene(SNCA) (rs2736990, OR=1.23, p=2.24×10−16) and at the MAPT locus (rs393152, OR=0.77, p=1.95×10−16). We exchanged data with colleagues performing a GWAS in Asian PD cases. Association at SNCA was replicated in the Asian GWAS1, confirming this as a major risk locus across populations. We were able to replicate the effect of a novel locus detected in the Asian cohort (PARK16, rs823128, OR=0.66, p=7.29×10−8) and provide evidence supporting the role of common variability around LRRK2 in modulating risk for PD (rs1491923, OR=1.14, p=1.55×10−5). These data demonstrate an unequivocal role for common genetic variability in the etiology of typical PD and suggest population specific genetic heterogeneity in this disease.

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supporting

confidence: 54%

Genome-wide association study reveals genetic risk underlying Parkinson's disease

et al. 2009

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“…35 Another study found AD patients who are tau H1/H1 haplotype carriers have lower CSF tau levels as compared to H1/H2 carriers. 36 We did not observe either effect but differences in sample size, age, and gender distribution may have influenced our findings since the gender effect was not present in the AD2 group.…”

Section: Discussionmentioning

confidence: 55%

Divergent CSF alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy

Wagshal

Sankaranarayanan

Guss

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

113

119

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Background Elevated CSF tau is considered a biomarker of neuronal injury in newly developed Alzheimer’s disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of tau species in other primary tauopathies. We assessed CSF tau protein abnormalities in AD, a tauopathy with prominent Aβ pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterized by deposition of four microtubule binding repeat (4R) tau with minimal Aβ pathology. Methods 26 normal control (NC), 37 AD, and 24 PSP patients participated in the study. AD and PSP were matched for severity using the clinical dementia rating sum of boxes (CDR-sb) scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF Aβ, total tau, and ptau181. Additional, novel ELISAs targeting different N-terminal and central tau epitopes were developed to examine CSF tau components and to investigate interactions between diagnostic group, demographics, and genetic variables. Results PSP had lower CSF N-terminal and C-terminal tau concentrations than NC and AD measured with both the novel tau ELISAs and the standard AlzBio3 tau and ptau assays. AD had higher total tau and ptau levels than NC and PSP. There was a gender by diagnosis interaction in both AD and PSP for most tau species, with lower concentrations for male compared to female patients. Conclusions CSF tau fragment concentrations are different in PSP compared with AD despite the presence of severe tau pathology and neuronal injury in both disorders. CSF tau concentration likely reflects multiple factors in addition to the degree of neuronal injury.

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“…19 Two studies showed an over-representation of H1 haplotype in FTD, 7,8 whereas other studies fail to find any relation with the haplotypes and the risk for the disease. 56,57 Therefore, H1…”

Section: -52mentioning

confidence: 99%

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

et al. 2008

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The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD. We aimed to investigate the association between MAPT haplotype status and brain morphology in healthy adults. A total of 150 healthy subjects underwent 3D high-resolution magnetic resonance (MR). MR images were processed following an optimized protocol to perform the Voxel-based morphometry (VBM) comparisons of the gray matter (GM) in H1 carriers (n ¼ 141) in contrast to H2H2 homozygous (n ¼ 9), and H1H1 homozygous (n ¼ 85) in contrast to H2 carriers (n ¼ 65). The threshold for statistical significance was 0.005 uncorrected. Opposite comparisons were also carried out. The groups had similar demographic and cognitive features. Compared with H2H2, the H1 carriers showed up to 19% smaller GM volume in the head of the right caudate nucleus, in the right middle frontal gyrus, in the left insula and orbito-frontal cortex, and in the inferior temporal and inferior cerebellar lobes, bilaterally. Compared with all H2 carriers, H1H1 displayed lower GM in the same regions, but the effect was smaller (5%), possibly due to a dilution effect by H1 in the H2 carriers group. The data suggest that H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies.

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<i>TAU</i> Haplotype and the <i>Saitohin</i> Q7R Gene Polymorphism Do Not Influence CSF Tau in Alzheimer’s Disease and Are Not Associated with Frontotemporal Dementia or Parkinson’s Disease

Cited by 21 publications

References 98 publications

Genome-wide association study reveals genetic risk underlying Parkinson's disease

Genome-wide association study reveals genetic risk underlying Parkinson's disease

Divergent CSF alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

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