Why looking at the whole hippocampus is not enough—a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer’s disease diagnosis

Abstract

The hippocampus is one of the earliest affected brain regions in Alzheimer’s disease (AD) and its dysfunction is believed to underlie the core feature of the disease-memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

“…Lastly, hippocampus-related disorders cannot be solely studied from the interesting but narrow perspective of structural imaging, and it is certain that multimodal imaging would provide additional and complementary information on the cerebral basis of cognitive disorders (Hedden and Growdon, 2014;La Joie et al, 2014b;Maruszak and Thuret, 2014). In the coming years, the combined use of subfield-centered task-related functional MRI ( …”

“…While most of the imaging literature has studied the hippocampus as a single unitary entity, it is acknowledged that this structure is heterogeneous and can be divided into subregions with different functions, connectivity to other brain regions and vulnerability to disease (Aggleton, 2012;Maruszak and Thuret, 2014;Small et al, 2011). This heterogeneity is found both along the anterior-posterior axis of the hippocampus and across its different cytoarchitectonic subfields, which include the cornu ammonis fields (CA1-CA4 2 ), the dentate gyrus (DG), and the subiculum.…”

FGWAS: Functional genome wide association analysis

“…Specifically, only a few top genes have similar rank information on the left and right hippocampal surfaces, indicating that hippocampal asymmetry exists. In fact, the hippocampus was found to be structurally and functionally asymmetric in both healthy adults and AD patients (Shi et al, 2009; Maruszak and Thuret, 2013). Furthermore, different gene-environment interaction effects are found on different hippocampal subfields (Rabl et al, 2014).…”

2015: Which new directions for Alzheimer's disease?

“…Nowadays, many AD molecular patterns have been screened to identify a potential therapeutic strategy. Although a myriad of evidence shows that the hippocampal volume decrease belongs to the AD earliest signs, as it is pointed out by the authors of the review paper presented in this issue, this element clearly could not be used as a diagnostic criterion (Maruszak and Thuret, 2014).…”

“…Nowadays, many AD molecular patterns have been screened to identify a potential therapeutic strategy. Although a myriad of evidence shows that the hippocampal volume decrease belongs to the AD earliest signs, as it is pointed out by the authors of the review paper presented in this issue, this element clearly could not be used as a diagnostic criterion (Maruszak and Thuret, 2014).With the flood of evidence for tau pathology as key event of the disease development, the understanding of diverse tau functions and its molecular behavior is one of the major steps in the progression of our knowledge about the neurodegenerescence detected in AD. The precision of tau role in DNA protection and RNA integrity under physiological conditions or under ROSproducing stress (Violet et al, 2014) provides clarification for a mechanistic model in which tau disturbance initiates an explanation for DNA damages observed in AD.…”