At least three key genetic mutations have been identified. One set of mutations involves genes encoding for tau, a protein found in neurofibrillary tangles both in some forms of frontotemporal dementias and in Alzheimer's disease. More recently, two other proteins have been identified: progranulin, a growth factor, and TDP-43, a cellular protein implicated in both frontotemporal dementias and amyotrophic lateral sclerosis. The gene encoding for familial frontotemporal lobar degenerations has yet to be identified, Dr. Knopman noted.
Although the pathologic changes vary, they may include accumulation of abnormal tau in neurons, leading to disruption of neuronal processes and apoptosis, progressive of loss of frontal and temporal neurons, gliosis and vacuolation. Amyloid deposits, a hallmark of Alzheimer's disease, are not typically seen in frontotemporal dementias, however.
| Neither Dr. Morris nor Dr. Knopman disclosed conflicts of interest relevant to this article. |
