Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease

Objective:To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer’s disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).Methods:CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied ‘target’ objects, novel ‘foil’ objects, and perceptually similar ‘lure’ objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Results:Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Conclusions:Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.

Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model

Alzheimers disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. To date, therapies targeting end-stage disease plaques, tangles, or inflammation have limited efficacy. Therefore, we set out to identify an earlier targetable phenotype. Utilizing a mouse model of AD and human fetal cells harboring mutant amyloid precursor protein, we show cell intrinsic neural precursor cell (NPC) dysfunction precedes widespread inflammation and amyloid plaque pathology, making it the earliest defect in the evolution of disease. We demonstrate that reversing impaired NPC self-renewal via genetic reduction of USP16, a histone modifier and critical physiological antagonist of the Polycomb Repressor Complex 1, can prevent downstream cognitive defects and decrease astrogliosis in vivo. Reduction of USP16 led to decreased expression of senescence gene Cdkn2a and mitigated aberrant regulation of the BMP pathway, a previously unknown function of USP16. Thus, we reveal USP16 as a novel target in an AD model that can both ameliorate the NPC defect and rescue memory and learning through its regulation of both Cdkn2a and BMP signaling.

The Remember Balloons by J. Oliveros

Oliveros, Jessie. The Remember Balloons. Illustrated by Dana Wulfekotte, Simon & Schuster Books for Young Children – Simon and Schuster, 2018 This beautifully written story tells of a young boy and his dear relationship with his aging Grandfather. Connected through balloons that hold memories and stories, the young boy notices his Grandfather begins to lose his balloons and eventually his memory, even of knowing his beloved grandson. Confused and upset, the young boy cannot understand why this is happening and tries in vain to save his Grandfather’s balloons. Saddened, the boy seeks his parent’s help whereby they show him that he now has a whole new set of balloons—his Grandfather’s. In acquiring these treasured memories, the young boy discovers a new way to be with his Grandfather through retelling him all his old stories. Illustrated in pencil sketch with minimal colour other than the varied and vibrant balloons, Oliveros speaks to children in a beautifully relatable manner about memories and stories and the connections to the people we cherish. It gently acknowledges the difficult changes in relationships as a loved one experiences the changes of aging and memory loss and guides the reader to find new ways to experience their stories and build new connections. The subtle acknowledgement of mixed-race families and friend groups also lends itself to a realistic and contemporary view of family and culture, further strengthening the relatability of this story to a wider readership. Recommended and appropriately written for ages 5-9 years, the book’s themes of keeping our memories close in our varied balloons and maintaining our connections with family even as relationships change, lends itself to a far greater age demographic. Highly recommended: 4 out of 4 stars Reviewer: Deanna Townsend Deanna Townsend is currently an Open Studies student and prospective graduate student with the Master of Library and Information Studies program at the University of Alberta. She is currently working in the Learning Commons/Library of an Elementary-Junior High School with Edmonton Public School Board. Her keen area of interest is in the transformation of school libraries/learning commons to modern, usable education spaces that inspire children to explore and learn beyond the classroom.