Journal of Alzheimer's Disease - Volume 66, issue 2

Authors: Salas, Isabel H. | Callaerts-Vegh, Zsuzsanna | D’Hooge, Rudi | Saido, Takaomi C. | Dotti, Carlos G. | De Strooper, Bart

Article Type: Research Article

Abstract: Commonly used Alzheimer’s disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL ), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old AppNL /NL mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits.

Keywords: Aging, Alzheimer’s disease, amyloid plaques, behavior, cognition, knock-in

DOI: 10.3233/JAD-180410

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 801-809, 2018

Authors: Müller-Ehrenberg, Lisa | Riphagen, Joost M. | Verhey, Frans R.J. | Sack, Alexander T. | Jacobs, Heidi I.L. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Measures of amyloid-β (Aβ) and phosphorylated tau (p-tau) concentrations in cerebrospinal fluid are extensively used for diagnostic and research purposes in Alzheimer’s disease (AD) as correlates of cortical thinning and cognitive outcomes. The present study investigated the relationship of Aβ and p-tau with hippocampal subfield volumes Cornu Ammonis (CA) 1–4, dentate gyrus (DG), and subiculum. Subfields were segmented from T1-weighted images from the ADNI-population using FreeSurfer v6. Linear and polynomial regression models revealed distinct associations of Aβ and p-tau with subfield volumes. Aβ had a quadratic relationship with all hippocampal subfield volumes and the inflection point was higher than the …validated cut-off for Aβ. For p-tau the relationships were linear, except for CA3, in which it was quadratic. For the CA1 and CA3, these quadratic relationships with Aβ were only observed when p-tau was low. Amyloid and p-tau contributed equally to the explained variance in CA4 and DG volume. Subicular volume was best explained by Aβ alone. These biomarker relationships with hippocampal subfield volumes seem to mirror the hippocampal-specific topography of Aβ and tau reported in neuropathological staging models. In addition, using continuous values of Aβ reveals positive patterns with imaging markers for individuals around the positivity threshold that would be masked when using dichotomized biomarker groups, which can be important for early detection and accurate inclusion of potential participants at risk for AD in clinical trials. Show more

Keywords: Aging, Alzheimer’s disease, amyloid, hippocampus, polynomial, subfields, tau

DOI: 10.3233/JAD-180676

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 811-823, 2018

Authors: Zotcheva, Ekaterina | Bergh, Sverre | Selbæk, Geir | Krokstad, Steinar | Håberg, Asta Kristine | Strand, Bjørn Heine | Ernstsen, Linda

Article Type: Research Article

Abstract: Background: Physical activity (PA) is associated with a decreased dementia risk, whereas psychological distress (distress) is linked to an increased dementia risk. Objective: We investigated independent and joint associations of midlife moderate-to-vigorous PA (MVPA) and distress with incident dementia. Methods: Our study comprised 28,916 participants aged 30–60 years from the Nord-Trøndelag Health Study (HUNT1, 1984–1986). Data on MVPA and distress from HUNT1 was linked to the Health and Memory Study in Nord-Trøndelag for dementia case identification. Participants were followed from 1995 until 2011. We used adjusted Cox regression models to estimate hazard ratios …(HRs) and 95% confidence intervals (95% CI). Results: In fully adjusted analyses, MVPA was associated with a reduced dementia risk (HR 0.81, 95% CI 0.62–1.06), compared to no MVPA. Distress was associated with an increased dementia risk (HR 1.30, 95% CI 0.99–1.70). Compared to distressed participants not taking part in MVPA, non-distressed no-MVPA participants had a reduced dementia risk (HR 0.72, 95% CI 0.54–0.96). The same applied to distressed MVPA participants (HR 0.50, 95% CI 0.22–1.14), and non-distressed MVPA participants (HR 0.63, 95% CI 0.44–0.90). Our results indicated an additive interaction between MVPA and distress on dementia risk. Conclusion: Our results suggest that midlife MVPA reduces risk of incident dementia among both distressed and non-distressed individuals. Show more

Keywords: Anxiety, cognition, dementia, depression, exercise, psychological stress

DOI: 10.3233/JAD-180768

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 825-833, 2018

Authors: Ryan, Margaret M. | Guévremont, Diane | Mockett, Bruce G. | Abraham, Wickliffe C. | Williams, Joanna M.

Article Type: Research Article

Abstract: Pathological changes underlying Alzheimer’s disease (AD) begin decades before the classical symptoms of memory loss become evident. As microRNAs are released from neurons and enter the bloodstream, circulating microRNAs may be reflective of AD progression and are ideal candidates as biomarkers for early-stage disease detection. Here, we provide a novel, in-depth analysis of how plasma microRNAs alter with aging, the most prominent risk factor for AD, and with development of amyloid-β (Aβ) plaque deposition. We assessed the circulating microRNAs in APPswe/PSEN1dE9 transgenic mice and wild-type controls at 4, 8 and 15 m (n = 8–10) using custom designed Taqman …arrays representing 185 neuropathology-related microRNAs. We performed a linear mixed-effects model to investigate the effects of age and genotype on plasma microRNAs expression. Following this analysis, we found 8 microRNAs were significantly affected by age alone in wild-type animals and 12 microRNAs altered in APPswe/PSEN1dE9 mice, either prior to Aβ plaque deposition (4 m) or during the development of AD-like pathogenesis (8 m or 15 m). Importantly, we found that differing sets of microRNAs were identified at each time point. Functional analysis of these data revealed that while common biological pathways, such as Inflammatory Response , were enriched throughout the disease process, Free Radical Scavenging, Immunological Disease , and Apoptosis Signaling were specifically enriched later in the disease process. Overall, this study reinforces that distinct biological processes underpin the early versus late stages of AD-like pathogenesis and highlights potential pre-symptomatic microRNAs biomarkers of neurodegeneration. Show more

Keywords: Aging, Alzheimer’s disease, circulating microRNAs, real-time polymerase chain reaction, transgenic mice

DOI: 10.3233/JAD-180385

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 835-852, 2018

Authors: Bamji-Mirza, Michelle | Li, Yan | Najem, Dema | Liu, Qing Yan | Walker, Douglas | Lue, Lih-Fen | Stupak, Jacek | Chan, Kenneth | Li, Jianjun | Ghani, Mahdi | Yang, Ze | Rogaeva, Ekaterina | Zhang, Wandong

Article Type: Correction

DOI: 10.3233/JAD-189009

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 853-854, 2018

Authors: Sigurdsson, Einar M.

Article Type: Correction

DOI: 10.3233/JAD-189010

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 855-856, 2018