Papers by Alexandra Trelle
Alzheimer's & Dementia
Alzheimer's & Dementia
Alzheimer's Research & Therapy
Background The recent promise of disease-modifying therapies for Alzheimer’s disease (AD) has rei... more Background The recent promise of disease-modifying therapies for Alzheimer’s disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation. Methods We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer’s Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluat...
There are currently limited molecular markers of Parkinson's disease, and there is an urgent ... more There are currently limited molecular markers of Parkinson's disease, and there is an urgent need for new markers to guide clinical care, support earlier diagnosis, and hasten drug development. Here, we performed CSF and plasma proteomics in 5 Parkinson's disease cohorts to identify novel protein biomarkers for these purposes, resulting in one of the largest such resources for Parkinson's disease to date. We discovered a consistent upregulation of the protein L-Aromatic Acid Decarboxylase (AADC, EC 4.1.1.28, DDC) in the CSF and plasma of Parkinson's disease patients. AADC is a key protein in the synthesis of dopamine and other monoamine neurotransmitters. We found that higher CSF AADC levels are associated with greater motor symptom severity in Parkinson's patients. We replicated and extended these findings in another undescribed proteomics cohort of de novo Parkinson's disease participants from the Parkinson's Progression Marker Initiative, where we foun...
Cognitive tests sensitive to the integrity of the medial temporal lobe (MTL), such as mnemonic di... more Cognitive tests sensitive to the integrity of the medial temporal lobe (MTL), such as mnemonic discrimination of perceptually similar stimuli, may be useful early markers of risk for cognitive decline in older populations. Perceptual discrimination of stimuli with overlapping features also relies on MTL, but remains relatively unexplored in this context. We assessed mnemonic discrimination in two test formats (Forced Choice, Yes/No) and perceptual discrimination of objects and scenes in 111 community-dwelling older adults at different risk status for cognitive impairment based on neuropsychological screening. We also investigated associations between performance and MTL subregion volume and thickness. The at-risk group exhibited reduced entorhinal thickness and impaired perceptual and mnemonic discrimination. Perceptual discrimination impairment partially explained group differences in mnemonic discrimination and correlated with entorhinal thickness. Executive dysfunction accounted ...
Alzheimer's & Dementia, 2021
The structure and computations associated with specific hippocampal subfields decline in aging an... more The structure and computations associated with specific hippocampal subfields decline in aging and are also initial sites of Alzheimer’s disease pathology. The degree to which age‐associated changes in hippocampal‐dependent memory are driven by early AD pathology among older normal adults remains unclear.
Alzheimer's & Dementia, 2021
The prevalence of amyloid positivity among diverse groups of clinically asymptomatic older indivi... more The prevalence of amyloid positivity among diverse groups of clinically asymptomatic older individuals is underexplored, especially in the context of prevention trials of Alzheimer’s disease (AD). We sought to determine whether rates of amyloid‐positivity differ in non‐Hispanic Asian individuals from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) study as compared to non‐Hispanic White individuals.
Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in m... more Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in memory, is a hallmark of cognitive ageing, characterised by a stark age-related increase in false recognition. While individual differences in mnemonic discrimination have gained attention due to potential relevance for early detection of Alzheimer’s disease (AD), our understanding of the component processes that contribute to variability in task performance across older adults remains limited. The present investigation explores the roles of representational quality, indexed by perceptual discrimination of objects and scenes with overlapping features, and strategic retrieval ability, indexed by standardized tests of executive function, to mnemonic discrimination in a large cohort of older adults (N=124). We took an individual differences approach and characterised the contributions of these factors to performance under Forced Choice (FC) and Yes/No (YN) recognition memory formats, which p...
European Journal of Nuclear Medicine and Molecular Imaging, 2020
Purpose In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is cr... more Purpose In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). Methods Forty-nine participants were scanned with 18 F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. Results SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18 F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. Conclusion Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18 F-PI-2620 in patients along the AD trajectory. This work confirms that 18 F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.
Age-related episodic memory decline is characterized by striking heterogeneity across individuals... more Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100; 60-82 yrs) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that hippocampal activity predicted cortical reinstatement strength, and these two metrics of pattern completion independently predicted retrieval success. However, increased age weakened cortical reinstatement and its relationship to memory behaviour. Critically, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple as...
Alzheimer's & Dementia, 2018
Blood labeling duration (LD) and postlabeling delay (PLD) design in the experiments T1 t2 t3 t4 t... more Blood labeling duration (LD) and postlabeling delay (PLD) design in the experiments T1 t2 t3 t4 t5 t6 t7 t8 t9 t10 t11 t12
Alzheimer's & Dementia, 2018
P4-322 THE CONTRIBUTION OF EARLY ALZHEIMER’S DISEASE MARKERS TO INDIVIDUAL DIFFERENCES IN EPISODI... more P4-322 THE CONTRIBUTION OF EARLY ALZHEIMER’S DISEASE MARKERS TO INDIVIDUAL DIFFERENCES IN EPISODIC MEMORY IN COGNITIVELY NORMAL OLDER ADULTS Alexandra N. Trelle, Jeffrey Bernstein, Valerie A. Carr, Gayle Deutsch, Carolyn A. Fredericks, Scott A. Guerin, Wanjia Guo, Marc Harrison, Manasi Jayakumar, Jiefeng Jiang, Geoffrey A. Kerchner, Anna Khazhenzon, Celia Litovsky, Beth C. Mormino, Ayesha Nadiadwala, Sharon Sha, Natalie Tanner, Monica Thieu, Anthony D. Wagner, Stanford University, Stanford, CA, USA; University of California San Diego, San Diego, CA, USA; San Jose State University, San Jose, CA, USA; Stanford Hospital and Clinics, Palo Alto, CA, USA; Genentech, Inc, South San Francisco, CA, USA; Johns Hopkins University, Baltimore, MD, USA; Massachusetts General Hospital, Boston, MA, USA; University of California at Irvine, Irvine, CA, USA; Stanford University, Palo Alto, CA, USA; Columbia University, New York, NY, USA. Contact e-mail: [email protected]
Mounting behavioral evidence suggests that declines in both representational quality and controll... more Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates, and changes in regional BOLD activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events, and increased pattern similarity between distinct events. During retrieval, both groups exhibited increased recruitment of areas within the core recollection network, including the hippocampus and angular gyrus, when endorsing studied pairs, whereas younger adults exhibited in...
Learning & memory (Cold Spring Harbor, N.Y.), 2018
The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the ... more The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments in hippocampal-dependent tasks. However, evidence for the opposite pattern following medial dorsal nuclei damage has not yet been identified. In the present study, we investigated recognition memory in NC, a patient with relatively selective medial dorsal nuclei damage, using two object recognition tests with similar foils: a yes/no (YN) test that requires the hippocampus, and a forced choice corresponding test (FCC) that is supported by perirhinal cortex. NC performed normally in the YN test, but was impaired in the FCC test. Critically, FCC performance was impaired only when the study-test delay period was filled with interference. We int...
Journal of Experimental Psychology: Learning, Memory, and Cognition, 2017
In a Yes/No object recognition memory test with similar lures, older adults typically exhibit ele... more In a Yes/No object recognition memory test with similar lures, older adults typically exhibit elevated rates of false recognition. However, the contributions of impaired retrieval, relative to reduced availability of target details, are difficult to disentangle using such a test. The present investigation sought to decouple these factors by comparing performance on a Yes/No (YN) test to that on a Forced Choice (FC) test, which minimizes demands on strategic retrieval processes, enabling a more direct measure of the availability of object details. Older adults exhibited increased lure false recognition across test formats (Experiment 1), suggesting a decline in the availability of object details contributes to deficits in performance. Manipulating interference by varying the number of objects studied selectively enhanced performance in the FC test, resulting in matched performance across groups, whereas age differences in YN performance persisted (Experiment 2), indicating an additional contribution of impaired strategic retrieval. Consistent with differential sensitivity of test format to strategic retrieval and the quality of stimulus representations among older adults, variability in the quality of object representations, measured using a perceptual discrimination task, was selectively related to FC performance. In contrast, variability in memory control processes, as measured with tests of recall and executive function, was related to performance across test formats. These results suggest that both declines in the availability of object details and impaired retrieval of object details contribute to elevated rates of lure false recognition with age, and highlight the utility of test format for dissociating these factors in memory-impaired populations.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 22, 2014
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Papers by Alexandra Trelle