Home > Neurology > Neuroinflammation common in familial frontotemporal dementia

Neuroinflammation common in familial frontotemporal dementia

Journal of Neurology, Neurosurgery and Psychiatry
Reuters Health - 26/11/2020 - Neuroinflammation appears to be a typical feature of the three most common monogenic forms of familial frontotemporal dementia (FTD), according to a new case series from the U.K.

Based on this finding, the authors suggest that "future disease-modifying treatment strategies may be enhanced by immunomodulation" and that positron emission tomography (PET) studies in presymptomatic carriers of one of the three genes "could help develop early, targeted, interventions."

One-fifth of FTD cases are autosomal dominant and typically arise from mutations in the GRN, MAPT or C9orf72 genes, Dr. James Benedict Rowe of the University of Cambridge and colleagues note in the Journal of Neurology, Neurosurgery and Psychiatry.

Some evidence, they add, suggests that neuroinflammation may be an early pathogenic process, rather than a result of neurodegeneration. In a previous PET study by some of the researchers, neuroinflammation in one form of FTD appeared before the onset of symptoms (https://bit.ly/3nEjTMa).

To learn more, the team used PET with the radioligand (11C)PK11195, which binds to activated microglia and measures neuroinflammation, in seven patients with symptomatic familial FTD from MAPT, GRN or C9orf72 mutations. They also quantified the distribution of tau or TDP-43 pathology, indexed using the radioligand (18F)AV-1451.

The patients - four women and three men - ranged in age from 51 to 70 at presentation. Common symptoms included behavioral changes, obsessional or paranoid behavior, apathy, language or cognitive deficits, and hoarding of sweets.

Across all mutation groups, the patients showed increased (11C)PK11195 binding, mostly in frontotemporal regions but with additional regions showing abnormalities in some individuals.

Carriers of GRN and C9orf72 mutations showed heterogeneous distributions of (18F)AV-1451 binding, while those with MAPT mutations had a consistent distribution across the brain.

Dr. Rowe told Reuters Health by email that FTD has usually been under way for 10 to 20 years before symptoms appear, providing a potential window during which to screen for faulty genes. The variation in where inflammation occurs determines the exact symptoms, he added.

One reason the role of inflammation in FTD has not been recognized earlier is the high cost of PET, which has been an obstacle to research in this area, Dr. Rowe noted.

Based on the new findings, he said clinical trials of targeted anti-inflammatories or immune therapies are warranted, perhaps involving therapies that were developed to treat other disorders.

Dr. Jillian Kril of the School of Medical Sciences at the University of Sydney, Australia, who has studied neuroinflammation in FTD, told Reuters Health by email that the new series adds to the increasing evidence showing that brain inflammation is an important aspect of FTD.

Although this is also true of other neurodegenerative diseases where histological examination reveals neuroinflammation, she continued, "the situation in FTD is somewhat more complex, as FTD shows marked clinical, pathological, and genetic heterogeneity."

This is unlike Alzheimer's disease, added Dr. Kril, who was not involved in the new work, where most patients exhibit a similar clinical profile and have similar neuropathology.

The new findings indicating shared inflammatory processes underlying genetically different types of FTD are helpful, she said, because they suggest "that rather than having to develop a range of therapies for FTD of differing causes, a single therapy that subdues neuroinflammation may be beneficial."

Furthermore, as neuroinflammation is the basis of some other neurological disorders, such as multiple sclerosis, there might already be therapies available that can be applied to FTD, she suggested.

The study had no commercial funding.

SOURCE: https://bit.ly/36LKVdO Journal of Neurology, Neurosurgery and Psychiatry, online October 29, 2020.

By Scott Baltic

Posted on