TY - JOUR
T1 - Going round in circles – the Papez Circuit in Alzheimer’s Disease
AU - Forno, Gonzalo
AU - Lladó, Albert
AU - Hornberger, Michael
N1 - Funding information: Departament de Salut de la Generalitat de Catalunya, Grant/Award Number: PERIS 2016-2020 SLT008/18/00061
PY - 2021/11
Y1 - 2021/11
N2 - The hippocampus is regarded as the pivotal structure for episodic memory symptoms associated with Alzheimer's disease (AD) pathophysiology. However, what is often overlooked is that the hippocampus is ‘only’ one part of a network of memory critical regions, the Papez circuit. Other Papez circuit regions are often regarded as less relevant for AD as they are thought to sit ‘downstream’ of the hippocampus. However, this notion is oversimplistic, and increasing evidence suggests that other Papez regions might be affected before or concurrently with the hippocampus. In addition, AD research has mostly focused on episodic memory deficits, whereas spatial navigation processes are also subserved by the Papez circuit with increasing evidence supporting its valuable potential as a diagnostic measure of incipient AD pathophysiology. In the current review, we take a step forward analysing recent evidence on the structural and functional integrity of the Papez circuit across AD disease stages. Specifically, we will review the integrity of specific Papez regions from at-genetic-risk (APOE4 carriers), to mild cognitive impairment (MCI), to dementia stage of sporadic AD and autosomal dominant AD (ADAD). We related those changes to episodic memory and spatial navigation/orientation deficits in AD. Finally, we provide an overview of how the Papez circuit is affected in AD diseases and their specific symptomology contributions. This overview strengthened the need for moving away from a hippocampal-centric view to a network approach on how the whole Papez circuit is affected in AD and contributes to its symptomology, informing future research and clinical approaches.
AB - The hippocampus is regarded as the pivotal structure for episodic memory symptoms associated with Alzheimer's disease (AD) pathophysiology. However, what is often overlooked is that the hippocampus is ‘only’ one part of a network of memory critical regions, the Papez circuit. Other Papez circuit regions are often regarded as less relevant for AD as they are thought to sit ‘downstream’ of the hippocampus. However, this notion is oversimplistic, and increasing evidence suggests that other Papez regions might be affected before or concurrently with the hippocampus. In addition, AD research has mostly focused on episodic memory deficits, whereas spatial navigation processes are also subserved by the Papez circuit with increasing evidence supporting its valuable potential as a diagnostic measure of incipient AD pathophysiology. In the current review, we take a step forward analysing recent evidence on the structural and functional integrity of the Papez circuit across AD disease stages. Specifically, we will review the integrity of specific Papez regions from at-genetic-risk (APOE4 carriers), to mild cognitive impairment (MCI), to dementia stage of sporadic AD and autosomal dominant AD (ADAD). We related those changes to episodic memory and spatial navigation/orientation deficits in AD. Finally, we provide an overview of how the Papez circuit is affected in AD diseases and their specific symptomology contributions. This overview strengthened the need for moving away from a hippocampal-centric view to a network approach on how the whole Papez circuit is affected in AD and contributes to its symptomology, informing future research and clinical approaches.
KW - anterior thalamic nucleus
KW - episodic memory
KW - hippocampus
KW - posterior cingulate cortex
KW - spatial navigation
UR - http://www.scopus.com/inward/record.url?scp=85118356665&partnerID=8YFLogxK
U2 - 10.1111/ejn.15494
DO - 10.1111/ejn.15494
M3 - Article
SN - 0953-816X
VL - 54
SP - 7668
EP - 7687
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 10
ER -