Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer’s disease

• Published in: Alzheimer's research & therapy 2021-05, Vol.13 (1), p.1-107, Article 107
• Main Authors: Yang, Jianwei, Kong, Chaojun, Jia, Longfei, Li, Tingting, Quan, Meina, Li, Yan, Lyu, Diyang, Li, Fangyu, Jin, Hongmei, Li, Ying, Wang, Qigeng, Jia, Jianping
• Format: Article
• Language: English
• Subjects: Accelerated long-term forgetting; Age; Alzheimer's disease; Asymptomatic; Biomarkers; Blood-borne factors; Cognition & reasoning; Cognitive ability; Complications and side effects; Dementia; Development and progression; Education; Genetic aspects; Memory; Memory, Disorders of; Mutation; Neurogenesis; Neuropsychology; Plasma; Proteins; Regression analysis; Risk factors; Senescence
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-021-00845-0

Background Accelerated long-term forgetting has been identified in preclinical Alzheimer's disease (AD) and is attributed to a selective impairment of memory consolidation in which the hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD). Methods We analyzed data of 39 asymptomatic participants (n = 18 ADAD mutation carriers, n = 21 non-carriers) from the Chinese Familial Alzheimer's Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min, and 7 days. Peripheral blood concentrations of candidate pro-aging factors (CC chemokine ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants. Results Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall ([beta] = -0.46, p = 0.002), figure recall ([beta] = -0.44, p = 0.004), and list recognition ([beta] = -0.37, p = 0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: [beta] = 0.39, p = 0.007; CCL11 versus list recognition: [beta] = 0.44, p = 0.002). Conclusions Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting. Keywords: Alzheimer's disease, Accelerated long-term forgetting, Blood-borne factors, Senescence, Biomarkers