Melissa E. Murray (United States of America)
Mayo Clinic Florida
Department of Neuroscience
Melissa E. Murray, Ph.D., leads the Translational Neuropathology laboratory in the Department of Neuroscience at Mayo Clinic in Florida. Dr. Murray holds the academic rank of Associate Professor of Neuroscience and has received numerous awards for her research that focuses on investigating the heterogeneity of Alzheimer’s disease (AD) with an emphasis on young-onset AD. She uses a multi-disciplinary approach to uncover neurobiologic differences underlying atypical and typical neuropathologic subtypes of AD and their relevance to clinical presentations observed antemortem. She received an R01 from the National Institute of Aging and an Alzheimer’s Association Research Grant to continue to pursue her research on atypical AD. Dr. Murray has published more than 200 scientific papers with the bulk of her studies centered on identifying the clinicopathologic characteristics and biomarkers of AD and related dementias. Her state of Florida funded initiatives seek to improve our understanding of ethnoracial differences in neuropathologic distribution and severity of AD and co-existing pathology. She is a co-PI of the multi-site Neuropathology Core for the Longitudinal Early Onset Alzheimer’s Disease Study (LEADS) and served as immediate past Chair for the International Society to Advance Alzheimer's Research and Treatment’s Atypical Alzheimer's disease Professional Interest Area group.

Moderator of 1 Session

 Conference Calendar
SYMPOSIUM

NEUROPATHOLOGY IN AD, LBD AND OTHER DEMENTIA & TRANSCRANIAL PULSE STIMULATION

Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
08:30 AM - 10:30 AM
Room
ONSITE: 133-134
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

LOCUS COERULEUS VULNERABILITY DIFFERS AMONG ALZHEIMER’S DISEASE NEUROPATHOLOGIC SUBTYPES AND MAY BE INFLUENCED BY YOUNGER AGE AT ONSET AND APOE

Session Name
0740 - APOE: MECHANISMS AND TREATMENT STRATEGIES 1 (ID 37)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 112
Lecture Time
03:30 PM - 03:45 PM
Presenter

Abstract

Aims

The locus coeruleus (LC) is a small pontine nucleus and primary source of norepinephrine in the human brain. In Alzheimer’s disease (AD), the LC is one of the first structures to accumulate hyperphosphorylated tau, resulting in marked reductions in size and volume. As the LC projects to and provides norepinephrine throughout corticolimbic structures, we aimed to examine the relationship of LC neuronal loss with corticolimbic patterns among AD subtypes and to investigate clinicopathologic predictors of LC neuronal loss.

Methods

Corticolimbic tangle patterns were used to classify AD subtypes as hippocampal sparing (HpSp), typical, and limbic predominant. An H&E-stained pons was digitally scanned and neuronal density measured in 783 AD cases.

Results

Among AD subtypes, limbic predominant had higher number of LC neurons compared to typical AD with HpSp AD having the fewest LC neurons (p=0.013). Multivariable regression analysis in typical AD accounted for 24% (R2=0.24) of the variability in LC neuronal loss (p<0.001): 10 years younger at death equated to 4 fewer LC neurons, 5 years longer in disease duration equated to 1 fewer neuron, and Braak tangle stage increase equated to 4 fewer neurons. No association was found between LC neuronal loss and sex, brain weight, or Thal phase. Interestingly, APOE ε4 status was associated with 2 more LC neurons.

Conclusions

Younger age onset, longer disease duration, and lack of an APOE ε4 allele may influence LC vulnerability. Our findings highlight the potential biomarker relevance of LC atrophy for young onset AD, which may inform corticolimbic tau patterns.

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