Progressive Memory Circuit Impairments along with Alzheimer's Disease Neuropathology Spread: Evidence from in vivo Neuroimaging.

During the progression of Alzheimer's disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A - T-; Group 1: CN, A + T-; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.