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NRN1 as a therapeutic target for Alzheimer's disease
by
Pugh, Derian A.
, Cary, Gregory A.
, Hobby, Emma L.
, Herskowitz, Jeremy H.
, Greathouse, Kelsey M.
, Seyfried, Nicholas T.
, Nassour‐Caswell, Lauren C.
in
aging
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Animals
/ antibody
/ Biomarkers
/ Brain
/ Brain - metabolism
/ Brain research
/ Candidates
/ Chloride
/ cognition
/ Dementia
/ Disease
/ Disease Models, Animal
/ GPI-Linked Proteins
/ Humans
/ Medical research
/ Mice
/ Mice, Transgenic
/ Neuroblastoma
/ Neurons
/ Neurons - metabolism
/ Neuropeptides
/ neurotrophic factor
/ Older people
/ Penicillin
/ Phosphatase
/ Proteins
/ Resilience
/ Sodium
/ tau Proteins - genetics
/ tau Proteins - metabolism
/ Therapeutic Assessment
/ Therapy
/ Tissues
2026
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NRN1 as a therapeutic target for Alzheimer's disease
by
Pugh, Derian A.
, Cary, Gregory A.
, Hobby, Emma L.
, Herskowitz, Jeremy H.
, Greathouse, Kelsey M.
, Seyfried, Nicholas T.
, Nassour‐Caswell, Lauren C.
in
aging
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Animals
/ antibody
/ Biomarkers
/ Brain
/ Brain - metabolism
/ Brain research
/ Candidates
/ Chloride
/ cognition
/ Dementia
/ Disease
/ Disease Models, Animal
/ GPI-Linked Proteins
/ Humans
/ Medical research
/ Mice
/ Mice, Transgenic
/ Neuroblastoma
/ Neurons
/ Neurons - metabolism
/ Neuropeptides
/ neurotrophic factor
/ Older people
/ Penicillin
/ Phosphatase
/ Proteins
/ Resilience
/ Sodium
/ tau Proteins - genetics
/ tau Proteins - metabolism
/ Therapeutic Assessment
/ Therapy
/ Tissues
2026
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NRN1 as a therapeutic target for Alzheimer's disease
by
Pugh, Derian A.
, Cary, Gregory A.
, Hobby, Emma L.
, Herskowitz, Jeremy H.
, Greathouse, Kelsey M.
, Seyfried, Nicholas T.
, Nassour‐Caswell, Lauren C.
in
aging
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Animals
/ antibody
/ Biomarkers
/ Brain
/ Brain - metabolism
/ Brain research
/ Candidates
/ Chloride
/ cognition
/ Dementia
/ Disease
/ Disease Models, Animal
/ GPI-Linked Proteins
/ Humans
/ Medical research
/ Mice
/ Mice, Transgenic
/ Neuroblastoma
/ Neurons
/ Neurons - metabolism
/ Neuropeptides
/ neurotrophic factor
/ Older people
/ Penicillin
/ Phosphatase
/ Proteins
/ Resilience
/ Sodium
/ tau Proteins - genetics
/ tau Proteins - metabolism
/ Therapeutic Assessment
/ Therapy
/ Tissues
2026
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Journal Article
NRN1 as a therapeutic target for Alzheimer's disease
2026
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Overview
INTRODUCTION Neuritin‐1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD). METHODS Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory‐Sage‐SGC‐JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT‐AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA‐AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models. RESULTS NRN1 has a TREAT‐AD target risk score of 3.29 out of 5. Based on single‐nucleus RNA sequencing from SEA‐AD, NRN1 expression in excitatory neurons tends to decrease with increasing donor pseudo‐progression. Abcam ab64186 polyclonal NRN1 antibody detects NRN1 protein in vitro and in vivo at molecular weights that suggest NRN1 forms a homodimer. NRN1 protein abundance is comparable among controls and primary tauopathy cases, as well as Tau P301S mice and non‐transgenic littermates at 3 and 9 months. DISCUSSION These findings advance the investigation of NRN1 as a therapeutic candidate for AD. Highlights NRN1 is associated with cognitive resilience to AD. Based on snRNA‐seq from SEA‐AD, NRN1 expression in excitatory neurons tends to decrease with increasing donor pseudo‐progression. Abcam ab64186 polyclonal NRN1 antibody detects NRN1 protein in vitro and in vivo at molecular weights that suggest NRN1 forms a homodimer. NRN1 protein abundance is comparable among controls and primary tauopathy cases, as well as Tau P301S mice and non‐transgenic littermates at 3 and 9 months.
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