TY  - CONF
AU  - Düzel, Emrah
AU  - Cikrikcili, Ugur
AU  - Schott, Björn H.
AU  - Jockschat, Thomas Nickl
AU  - Berron, David
AU  - Soch, Joram
AU  - Krohn, Friedrich
TI  - Amygdala Novelty Responses, Depressive Symptoms, and Tau Pathology in Preclinical Alzheimer's Disease: An fMRI Investigation
JO  - Alzheimer's and dementia
VL  - 21
IS  - S1
SN  - 1552-5260
M1  - DZNE-2025-01450
SP  - e107337
PY  - 2025
AB  - Background: Late-life depression (LLD) is a well-established risk factor for Alzheimer's disease (AD) and has been linked to cognitive decline. The amygdala, an important region for emotional regulation and novelty detection, is one of the earliest sites of tau accumulation in AD. However, it remains unclear how depressive symptoms and tau burden interact with amygdala function in preclinical AD stages. This study examines the relationship between amygdala novelty responses, depressive symptoms.Method:A total of 190 participants (HC = 58, SCD = 88, MCI = 44) underwent functional MRI (fMRI) to assess amygdala novelty responses. Depression severity was measured using the GDS, and tau pathology was classified based on CSF phosphorylated tau (p-Tau) and total tau (t-Tau) levels. Participants were further categorized based on depressive symptoms (GDS = 0 vs. GDS ≥1) and tau status (Tau (-) vs. Tau (+)) for statistical analyses.Result:Group comparisons revealed significantly higher GDS scores in SCD and MCI groups compared to HC (p < 0.05), reflecting increased depressive symptoms in individuals with cognitive complaints. However, no significant correlation was observed between amygdala novelty responses and GDS scores across diagnostic groups. Additionally, CSF tau levels (p-Tau and t-Tau) did not significantly interact with depressive symptoms in predicting amygdala responses. The lack of significant findings in amygdala response may be attributed to the relatively low overall severity of depressive symptoms in the sample, which could limit detectability of neural alterations.Conclusion: Although prior studies have indicated that late-life depression and tau pathology are associated with the progression of Alzheimer's disease (AD), our findings suggest that subclinical depressive symptoms do not significantly impact amygdala novelty responses in preclinical AD. The observed increase in depressive symptoms in SCD and MCI groups suggests that affective changes may still be an important factor in disease progression, but their relationship with amygdala function remains unclear. Future research should explore clinically significant depression, longitudinal changes in affective symptoms, and other neurobiological mechanisms, such as amyloid burden and neuroinflammation, to better understand the early neural changes associated with AD.
T2  - Alzheimer’s Association International Conference
CY  - 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2  - 27 Jul 2025 - 31 Jul 2025
M2  - Toronto, Canada
KW  - Humans
KW  - Male
KW  - Female
KW  - Amygdala: physiopathology
KW  - Amygdala: diagnostic imaging
KW  - Magnetic Resonance Imaging
KW  - tau Proteins: cerebrospinal fluid
KW  - Aged
KW  - Depression: physiopathology
KW  - Cognitive Dysfunction: physiopathology
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Alzheimer Disease
KW  - Middle Aged
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
DO  - DOI:10.1002/alz70855_107337
UR  - https://pub.dzne.de/record/283043
ER  -