Editorial: Alzheimer's Disease and the Fornix

The fornix is a white matter bundle that connects the hippocampus with other limbic structures. It appears in the literature as early as 1543 in a historical publication of De Humani Corporis Fabrica by Andreas Vesalius (Swanson, 2014). The fornix is important for episodic memory recall (Tsivilis et al., 2008), which is impaired in Alzheimer's disease (AD). Alterations in the fornix were first observed in post-mortem AD brains (Hopper and Vogel, 1976). This volume focuses on the role of the fornix, and other limbic fibers, in the disease mechanisms of AD with some attention to how this might be applied in clinical practice. The observation of limbic fibers in vivo forms a basis for understanding normal anatomy and alterations caused by various diseases. Mori and Aggarwal were able to observe the fornix, cingulum, and stria terminalis in mice and humans, using T1-weighted and diffusion tensor imaging. In adult human brains, the limbic fibers are known to connect the structures of the default mode network (DMN), but the development of these fibers is less well understood. Yu et al. demonstrated that the developmental curve of DTI-derived measures of fornix integrity appear logarithmic, with rapid changes until 2 years of age followed by slow changes until 25 years. Development of the cingulate cingulum is disproportionally rapid during this period, but development of the hippocampal cingulum and the fornix is proportional. Notably, the functional and anatomic connectivity of the DMN is already established in the early postnatal period. The fornix is among the white matter structures that mature early during development. Douet and Chang reviewed changes in DTI measures in the fornix during development and aging. Development of the fornix peaks in late adolescence, followed by pruning and then degeneration. Fractional anisotropy (FA) values correlate with cognitive performance in various age groups, including children, young adults, and the elderly. Correlations are seen in various brain diseases including schizophrenia, multiple sclerosis, Parkinson's, and epilepsy. Normal aging affects the anatomy of the fornix. Kantarci proposed a hippocampus-fornix axis in which microstructural alterations in both hippocampus and fornix affect each other. In AD, it is likely that neuronal damage in hippocampus and axonal damage in fornix affect each other, but alterations in the fornix in normal aging are likely the consequence of age-related, non-specific axonal and myelin damage. Less is known about the relationship between alterations in fornix and functional connectivity. Kehoe et al. investigated whether …