From the Guidelines
The MAPT gene is a crucial factor in the development of frontotemporal dementia (FTD), and genetic testing for MAPT mutations is recommended for individuals with a family history of early-onset dementia. The MAPT gene encodes the tau protein, which plays a significant role in stabilizing microtubules in neurons 1. Mutations in the MAPT gene can lead to abnormal tau protein production, causing it to form tangles inside brain cells that disrupt normal cellular function and lead to neurodegeneration. These tau tangles are a hallmark of several forms of dementia, including Alzheimer's disease, but MAPT mutations are specifically linked to familial forms of FTD 1.
Key Points to Consider
- Patients with MAPT mutations typically develop symptoms in their 40s or 50s, including personality changes, language difficulties, and behavioral problems 1.
- Currently, there are no medications that directly target MAPT mutations or tau pathology, though several are in clinical development 1.
- Treatment focuses on symptom management with medications like selective serotonin reuptake inhibitors for behavioral symptoms or antipsychotics for severe agitation 1.
- Genetic testing for MAPT mutations is available for those with a family history of early-onset dementia, and genetic counseling is recommended before testing due to the implications for family members 1.
Importance of Genetic Testing
Genetic testing for the three common genetic abnormalities of bvFTD (GRN, MAPT, and C9orf72) is currently indicated if at least one first-degree relative is affected 1. A positive family history should be considered to extend beyond FTD and young-onset dementia to include Parkinson’s disease or related disorders, ALS, and unexplained late-onset psychiatric disorders 1. Given the strong overlap with psychiatric phenotypes and the significant proportion of mutations in apparent sporadic cases, testing for the C9orf72 expansion is increasingly justified in every patient with a late-onset behavioral presentation 1.
Implications for Clinical Practice
Understanding the MAPT gene's role has been crucial for developing potential disease-modifying therapies targeting tau protein abnormalities 1. Genetic counseling is essential before testing due to the implications for family members, and patients should receive counseling on the implications of genetic testing 1.
From the Research
Mapt Gene in Dementia
- The MAPT gene is associated with frontotemporal dementia (FTD), a group of brain disorders caused by cell degeneration in the brain's frontal and temporal lobes 2, 3, 4, 5, 6.
- Mutations in the MAPT gene can cause FTD, with over 60 MAPT mutations identified to date, usually causing behavioral variant FTD and/or parkinsonism clinically 3.
- The clinical features of FTD caused by MAPT mutations include disinhibition, apathy, loss of empathy, and compulsions, with motor changes occurring later in the illness 2.
- MAPT mutations can also cause other neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and corticobasal syndrome 4, 6.
- Different MAPT mutations can give rise to distinct atrophy patterns and clinical phenotypes, providing insights into the underlying disease biology and potential utility for patient stratification in therapeutic trials 5.
- The MAPT gene is one of the major genes associated with FTD, along with GRN and C9orf72, and genetic testing can help diagnose FTD in patients with a family history of the disease 2.