MAPT rs9468 and A152T: Tau, Parkinson’s, and Dementia Genetics
Neurons depend on an internal transport network to move essential materials along their nerve fibers. Tau, the protein produced by the MAPT gene, helps maintain that network by supporting structures called microtubules [R].
MAPT genetics offers two different ways to explore this biology:
Understanding the distinction makes your results more informative: one marker identifies a broader inherited background, while the other changes a building block in tau itself.
Explore both in the free MAPT GeneExplorer entry.
What Does the MAPT Gene Do?
MAPT stands for microtubule-associated protein tau.
Microtubules form part of the cell’s structural framework and provide routes for transporting materials. Tau helps assemble and stabilize these structures, supporting the organization and function of neurons [R].
Tau is also central to tauopathies, conditions involving abnormal tau accumulation. These include progressive supranuclear palsy and several forms of frontotemporal degeneration. Tau pathology is also an important feature of Alzheimer’s disease.
Different diseases can involve different forms and distributions of tau. That helps explain why a genetic association with one condition does not automatically apply to every tau-related disorder [R].
MAPT rs9468: What Are H1 and H2?
A haplotype is a group of genetic variants that tend to be inherited together.
The MAPT region has two major inherited backgrounds, called H1 and H2. Researchers use markers such as rs9468 to distinguish them. Rs9468 lies in a noncoding region and does not change tau’s amino-acid sequence [R].
For this marker:
T tags the H1 background.
C tags the H2 background.
Rs9468 genotype | Haplotype interpretation | Parkinson’s research context |
TT | H1/H1 | Two H1-associated alleles; no H2-associated C allele. |
CT | H1/H2 | One H2-associated C allele, linked to lower Parkinson’s odds. |
CC | H2/H2 | Two H2-associated C alleles, linked to lower Parkinson’s odds. |
Source: [R].
H1/H1 is a common inherited background. It should not be interpreted as an abnormal tau protein or a diagnosis.
How Much Difference Did rs9468 Make in Research?
An Italian study examined 904 people with Parkinson’s disease and 891 controls.
After adjustment for sex, smoking, and coffee consumption, the rs9468 C allele was associated with approximately 31% lower Parkinson’s disease odds [R]. This is an allele-based association, not a separate validated percentage for each CT and CC genotype. It also does not mean a 31-percentage-point reduction in someone’s lifetime probability of developing Parkinson’s.
The broader haplotype relationship has support from other research. A separate study reported 46% higher Parkinson’s odds for H1/H1 compared with H1/H2 and H2/H2 combined, after adjusting for age, sex, and recruitment site [R].
Is MAPT H1 Also Relevant to Progressive Supranuclear Palsy?
Yes. The MAPT region is also strongly associated with progressive supranuclear palsy, or PSP, a condition affecting movement, balance, and eye movements. A large genetic investigation identified a particularly strong association at rs9468, reinforcing the importance of this region in PSP biology [R].
For another aspect of Parkinson’s genetics, explore LRRK2 rs34637584, also called G2019S.
MAPT rs143624519: What Is A152T?
A152T is a separate rare variant, not another name for H1 or H2.
It replaces alanine with threonine at position 152 in a commonly studied tau protein form. At the DNA level, the change is G to A [R].
Rs143624519 genotype | Interpretation |
GG | No A152T copies detected. |
AG | One A152T copy; associated with increased susceptibility to certain conditions in research. |
AA | Two A152T copies. Associated with increased susceptibility to certain conditions in research. |
A152T: What Have Dementia Studies Found?
A 2012 study examining 15,369 people reported the following associations among A152T carriers compared with noncarriers:
Condition | Reported odds ratio |
Frontotemporal dementia–spectrum disorders | 3.0 |
Alzheimer’s disease | 2.3 |
Source: [R].
A later independent study involving 3,100 patients and 4,351 controls supported increased susceptibility to frontotemporal dementia and progressive supranuclear palsy syndrome [R].
Research has also connected A152T with dementia with Lewy bodies. One study reported an odds ratio of 5.76, but its wide confidence interval—1.62–20.51—shows substantial uncertainty arising from the small number of carriers [R].
For related Alzheimer’s genetics, read about APOE, rs429358, and rs7412.
How Might A152T Change Tau Function?
Laboratory experiments found that A152T weakened tau’s interaction with microtubules and increased the formation of small tau clusters called oligomers [R].
A separate neuronal-model study linked A152T with impaired retrograde axonal transport—movement back along the axon toward the cell body [R].
The effects are not uniform across diseases. A 2026 study of 401 neuropathologically confirmed Pick’s disease cases found only one A152T carrier and did not support increased susceptibility to that particular tauopathy [R].
How to Read Your Two MAPT Results Together
The two markers answer different questions:
Rs9468: Which common H1/H2 background does your genotype tag?
Rs143624519: Does your file record the rare A152T protein-changing variant?
An H2-associated result does not cancel an A152T finding. Likewise, H1/H1 does not imply that you carry A152T. A152T is studied as a susceptibility variant, and its clinical classification remains unsettled. An apparent AG or AA result in consumer raw DNA should be clinically confirmed before informing medical or family decisions.
Explore Your MAPT Results in GeneExplorer
MAPT connects neuronal structure with two distinct forms of genetic variation: a common inherited background and a rare change in tau itself.
Visit the free MAPT GeneExplorer entry to explore rs9468 and A152T. You can analyze your existing raw DNA file in your browser to check which markers are available in your results.
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