Alzheimer’s disease and the fornix

Alzheimer’s disease (AD) is the most common form of neurodegenerative dementias. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that start form the entorhinal cortex and the hippocampus. In addition to these gray matter structures, histopathological studies indicate that the white matter is also a good target for both the early diagnosis of AD and for monitoring disease progression. The fornix is a white matter bundle that constitutes a core element of the limbic circuits, and one of the most important anatomical structures related to memory. The fornixes originate from bilateral hippocampi, merge at the midline of the brain, again divide into the left and right side, and then into the precommissural and the postcommissural fibers, and terminate at the septal nuclei, nucleus accumbens (precommissural fornix) and hypothalamus (postcommissural fornix). These functional and anatomical features of the fornix naturally gather researchers’ attention as a possible diagnostic and prognostic marker of AD. Indeed, neurodegeneration of the fornix is histologically observed in AD model mice, and growing evidence indicate that the alterations seen in the fornix is potentially a good marker to predict future conversion from mild cognitive impairment to, and even from cognitively normal individuals to, AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the functional marker. Moreover, there is an attempt to stimulate fornix to recover the cognitive function of AD, and the ongoing research indicated the effect to the brain metabolism that relate to the functional recovery.
This research topic primarily focuses on a role of the fornix in disease mechanisms and clinical practice of AD. We welcome review articles, original research, and methodological advances related to basic researches using animal models, histopathology, electrophysiology, and in- and ex-vivo imaging researches. In addition, we are also interested in the alterations of the fornix seen in other diseases or clinical conditions, which might affect the diagnostic specificity of the fornix alteration seen in AD. For example, fornix might be affected by tumors, infections, inflammations, metabolic abnormalities, infarction, malformations, and trauma, as well as neurodegeneration due to schizophrenia. We place a particular emphasis on the difference and similarity of the fornix alterations seen in AD and in other diseases.