@article {Berron1279-19, author = {David Berron and Arturo Cardenas-Blanco and Daniel Bittner and Coraline D. Metzger and Annika Spottke and Michael T. Heneka and Klaus Flie{\ss}bach and Anja Schneider and Stefan J. Teipel and Michael Wagner and Oliver Speck and Frank Jessen and Emrah D{\"u}zel}, title = {Higher CSF tau levels are related to hippocampal hyperactivity and object mnemonic discrimination in older adults}, elocation-id = {1279-19}, year = {2019}, doi = {10.1523/JNEUROSCI.1279-19.2019}, publisher = {Society for Neuroscience}, abstract = {Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTL). Tau pathology is frequently found within the MTL of older adults and therefore likely to affect mnemonic discrimination even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC) have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance and levels of total and phosphorylated tau as well as Aβ42/40 ratio in cerebrospinal fluid (CSF). We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus and both, increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline.SIGNIFICANCE STATEMENTSubregions in the human medial temporal lobe (MTL) are critically involved in episodic memory and at the same time affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related functional magnetic resonance imaging in combination with measures of tau pathology in cerebrospinal fluid, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/early/2019/09/18/JNEUROSCI.1279-19.2019}, eprint = {https://www.jneurosci.org/content/early/2019/09/18/JNEUROSCI.1279-19.2019.full.pdf}, journal = {Journal of Neuroscience} }