Neurons is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Neurons are the fundamental cellular units of the nervous system responsible for receiving sensory input and sending motor commands1. They are the primary cells involved in information processing, learning, memory, and all higher cognitive functions. In neurodegenerative diseases, neurons
are progressively lost, leading to cognitive and motor deficits2.
The cell body contains:
The study of Neurons has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Classified 2,420 scATAC-seq cells into 17 clusters including 8 excitatory and 4 inhibitory populations. Revealed Mef2c and Rora motifs enriched in PV interneurons (p < 10^-22 and p < 10^-9).
Model System: Mouse visual cortex: SMART-seq2 scRNA-seq (14,249 cells) and scATAC-seq gene activity matrix from prefrontal cortex
Statistical Significance: p < 10^-22 for Mef2c motif enrichment, p < 10^-9 for Rora
BANKSY delineated granular layer, Purkinje neurons, and MLIs more accurately than nonspatial clustering. Identified 8 clusters in Slide-seq v.2 corresponding to cell types vs 6 from nonspatial clustering. BANKSY yielded lower NCC scores confirming more contiguous clusters.
Model System: Mouse cerebellum Slide-seq v.1 and v.2 datasets
Statistical Significance: r=0.85 (BANKSY) vs r=0.44 (nonspatial) correlation with RCTD weights for granular layer
BANKSY separated CA3 neurons from SSC neurons and fornix from thalamic oligodendrocytes. Nonspatial and MERINGUE merged these subtypes. BANKSY identified region-specific cell types with subtly distinct transcriptomes. Validated with scRNA-seq using DEGs and guilt-by-association genes.
Model System: Mouse hippocampus VeraFISH data
Statistical Significance: Multiple comparisons across clustering resolutions (16-20 clusters)
Revealed role of astrocytes and microglia in unfolded protein response and cytokine signalling. CD4+ CTLs more prevalent with increased interferon-gamma response. Endothelial cells especially sensitive to IFNG.
Model System: Human midbrain specimens from PD patients and healthy individuals
Statistical Significance: Not applicable
Awuah Wireko Andrew et al., (2023)
Uncovered disease-specific gene expression changes and disrupted cellular pathways. Found high cytotoxic T cells, lower monocytes in ALS CSF. Identified novel CD8+ T-cell subtypes with varied stemness gene expression.
Model System: ALS patient-derived motor neurons, CSF samples
Statistical Significance: Not applicable
Awuah Wireko Andrew et al., (2023)
Identified 461 clusters and 3313 subclusters organized by developmental origins. Found unexpectedly high diversity of midbrain and hindbrain neurons (splatter neurons). Area-specific cortical neurons identified. Astrocytes exhibited regional diversity at multiple scales with telencephalon-specific and location-specific subtypes. Oligodendrocyte precursors comprised two distinct major types: Type 1 (telencephalon-specific) and Type 2 (non-telencephalon).
Model System: Human postmortem brain tissue from 3 donors (18-68 years, no neuropsychiatric conditions)
Statistical Significance: N/A - descriptive study
Confirmed RNA-seq findings spatially. Dopaminergic cells demarcated PBP, SN, and VTA. GABAergic cells distinguished SN pars compacta vs reticulata. Glutamatergic PVALB+ cells occupied red and pontine nuclei. Noradrenergic cells marked locus coeruleus. Spatial distributions matched RNA-seq clusters for lower rhombic lip neurons and CALB2+ dopaminergic cells. Revealed combinatorial neuropeptide and neurotransmitter expression patterns.
Model System: Fresh-frozen human postmortem brain tissue sections from midbrain and hindbrain regions
Statistical Significance: N/A
Validated presence of OTX2+, SOX14+, and CASR+ cells (midbrain-derived inhibitory neurons) in the efferent nuclei of the pons (PnEN). Confirmed localization of these marker genes in pontine regions.
Model System: Fresh-frozen human postmortem brain tissue from pons region
Statistical Significance: N/A
Identified 14 TH+ subtypes (vs 10 in Kamath et al.). Found 7 new TH+ subtypes including SOX6 LPL subtype in substantia nigra and 4 CALB1+ subtypes in periaqueductal grey and VTA. Identified third class of TH+ neurons co-expressing GABAergic markers (CALCR and EBF2 clusters).
Model System: Human midbrain dopaminergic neurons from this study vs published dataset
Statistical Significance: Cross-validation performed with varying parameters
EMBER distinctly discriminated tau deposits localized to neurons, astrocytes, and oligodendrocytes in PiD; neurons, astrocytes, and oligodendrocytes have distinct conformational strains in same brain; spatial resolution revealed cell-type specific strain variation
Model System: Pick's disease brain sections with tau inclusions in neurons, astrocytes, and oligodendrocytes
Statistical Significance: Cell-type specific cluster separation
Microglia expressed highest TLR5 levels; adult microglia expressed higher TLR5 than neonatal microglia; astrocytes and Oli-neu cells expressed low TLR5; TLR5 was barely detectable in cortical neurons
Model System: Primary neonatal microglia, adult microglia, astrocytes, and cortical neurons from C57BL/6 mice; Oli-neu oligodendroglial precursor cell line
Statistical Significance: P<0.05; P<0.01
TLR5 protein readily detectable in microglia and astrocytes (to lesser extent); not detected in cortical neurons; antibody specificity confirmed in Tlr5-/- mice
Model System: Cultured neonatal microglia, astrocytes, and neurons from C57BL/6 (WT) and Tlr5-/- mice
Flagellin induced neuronal loss in dose and time-dependent manner; 10ng/ml caused 19.2% loss (P=0.017); 100ng/ml caused 30.9% loss (P=0.0042) after 72h; neurons co-cultured with Tlr5-/- microglia protected; flagellin did not affect neurons in absence of microglia
Model System: Co-cultures of cortical neurons and microglia from WT or Tlr5-/- mice (ratio 8:1)
Statistical Significance: P<0.05; P<0.01 vs control
97% of cortical neurons express at least one NPP gene; 80% express at least one NPP at >1,000 CPM. Npy, Sst, Vip, and Tac2 rank as top 4 by pFPKM. Eleven of 18 NPP genes rank in top percentile of all protein-coding genes.
Model System: Mouse cortical neurons from primary visual cortex (VISp) and anterior lateral motor cortex (ALM)
Statistical Significance: N/A
Stephen J Smith et al., (2019)
98% of neurons express at least one NP-GPCR gene; 78% express at least one at >100 CPM. Most NP-GPCR genes expressed well above median for all protein-coding genes.
Model System: Mouse cortical neurons from VISp and ALM
Statistical Significance: N/A
Stephen J Smith et al., (2019)
47 NP genes achieve average RI = 0.925 for neuron type classification; 62% of neurons classified correctly at type level. This significantly exceeds random gene subsets (RI = 0.641 +/- 0.047) and expression-matched random subsets (RI = 0.843 +/- 0.027).
Model System: Mouse cortical neurons - 115 transcriptomic types from Tasic 2018 dataset
Statistical Significance: p<0.01 (bootstrap)
Stephen J Smith et al., (2019)
Modal number of co-expressed NPP genes is 2-5 per neuron; modal number of co-expressed NP-GPCR genes is 6. Multiple cognate NPP/NP-GPCR pairs commonly co-expressed in same neuron, suggesting possible autocrine signaling.
Model System: Mouse cortical neurons
Statistical Significance: N/A
Stephen J Smith et al., (2019)
Transcriptional changes strongest and highly cell-type-specific early in disease. Generalized activation of proteostasis and stress response genes in advanced disease. Sex-biased gene expression patterns in neurons and oligodendrocytes. Myelination-related processes recurrently altered across cell types.
Model System: Human postmortem prefrontal cortex
Statistical Significance: Not specified
Cláudio Gouveia Roque et al., (2024)
AD neurons accumulate 874 more somatic single-nucleotide variants on average than control cells (49% increase). Cytosine-to-adenine substitutions enriched in AD neurons, associated with oxidative damage. Base excision repair impaired in AD.
Model System: Human AD postmortem brain neurons
Statistical Significance: Not specified
Cláudio Gouveia Roque et al., (2024)
Cell-level overdispersion decreased with increasing gene expression. Subject-level overdispersion was largely attributed to subject-level covariates (age, sex, AD status). Cell-level overdispersion resulted from subpopulation heterogeneity. ~90% and ~80% of genes analyzed using NEBULA-LN alone in excitatory neurons (CPS~700) and oligodendrocytes (CPS~380).
Model System: Human postmortem brain tissue - 48 subjects from ROSMAP cohort
Statistical Significance: N/A - descriptive analysis
Successfully annotated snmC-seq profiles with high confidence using Allen Brain Atlas reference. RNA-assisted annotation provided clearer labels than unsupervised clustering (e.g., L6 neurons correctly labeled as near-projecting vs deep neocortical laminar 6b).
Model System: Human cortex snmC-seq dataset
Statistical Significance: Not applicable
85-90% of most predictive molecular pathways in brain were also top predictors in blood. Common pathways: blood coagulation, angiogenesis, p53, B cell activation, Wnt signaling. Brain cell types: astrocytes (38% ROSMAP, 22% HBTRC), microglia (4% ROSMAP, 48% HBTRC), oligodendrocyte precursor cells (35% ROSMAP, 17% HBTRC), neurons, endothelial cells.
Model System: ROSMAP and HBTRC brain tissues, ADNI blood
Statistical Significance: Not applicable (enrichment analysis)
T807 perfectly colocalized with tau-containing neurons and dystrophic neurites. Confirmed strong T807 binding to tau pathology in AD but not to cerebral amyloid, DLB, MSA, or TDP-43. Tangles and dystrophic neurites account for most of the in vivo T807 signal.
Model System: Human AD brain tissue
Statistical Significance: N/A
Hartmuth C. Kolb, José Ignacio Andrés (2017)
Most glutamatergic cell types shared among multiple areas with continuous gradients. Medial (RSP/ACA) and lateral (TEa-PERI-ECT) regions most distinct. Anterior-posterior transitions more continuous. IT neurons continuously distributed across cortical depth (L2/3 to L6).
Model System: Mouse isocortex - multiple cortical areas
Statistical Significance: N/A
Aβ molecular associates enriched in pyramidal cells (q=0.002, δ=3.804) and endothelial-mural cells (q=0.008, δ=2.950); tau associates enriched in interneurons (q=0.021, δ=2.834); Aβ∙tau signature highly enriched in microglia (q<0.001, δ=10.425)
Model System: Gene sets from transcriptomic analysis with single-cell data from mouse somatosensory cortex and hippocampus CA1
Statistical Significance: q < 0.05
Sanchez-Rodriguez et al., (2023)
Excitatory neurons had most eGenes (7,331), followed by inhibitory neurons (2,214), oligodendrocytes (1,968), astrocytes (1,705), OPCs (1,284), microglia (899), and endothelial cells (532). 46% of eGenes (4,598) were cell type-specific.
Model System: Human DLPFC - seven cell types: excitatory neurons, inhibitory neurons, astrocytes, microglia, oligodendrocytes, OPCs, endothelial cells
Statistical Significance: FDR < 0.05
234 of 6,414 (3.6%) eGenes replicated in iPSC-derived neurons; 121 of 2,529 (4.8%) replicated in astrocytes. Most eQTLs had same direction in vivo and in vitro. Exception: MAPT gene showed opposite direction of effect in iPSC-derived vs brain tissue.
Model System: iPSC-derived excitatory neurons and astrocytes from ROS/MAP participants
Statistical Significance: P<1x10-6 for replication above chance
11 PD risk loci colocalized with 13 eGenes. Excitatory neurons achieved the largest number of colocalized loci.
Model System: Human DLPFC cell types
Statistical Significance: PP.H4 > 0.8
57 SCZ loci colocalized with 75 eGenes. Excitatory neurons had largest number of colocalized loci.
Model System: Human DLPFC cell types
Statistical Significance: PP.H4 > 0.8
Most SCN neurons exhibit robust cell-autonomous limit cycle oscillations. Central SCN neurons show higher robustness (V approx 1) while surrounding tissues show noise-induced oscillations (V approx 0). Parameters Hill coefficient (n=3-8) and delay dispersion (2-5 hours) determine oscillator phenotype. Mean delay times for Cry1 oscillators estimated at 8-10 hours.
Model System: Organotypic mouse SCN slices expressing CRY1-LUC (three biological replicates)
Statistical Significance: Kolmogorov-Smirnov test with Bonferroni correction: 99.84% of locations accepted Gaussianity of residuals
LC neuronal loss averages 63% in AD; LC volume decreases by 8.4% per Braak stage increase; 8% of LC neurons are p-tau-positive at Braak stage 0, doubling by Braak stage I, reaching 100% by Braak stage VI; rostral portion affected more severely (83% loss) compared to middle (23%) and caudal (15%) parts
Model System: Human postmortem brain tissue
Statistical Significance: Significant correlation between LC volume loss and Braak stage (p<0.05)
Classified 2,420 scATAC-seq cells into 17 clusters including 8 excitatory and 4 inhibitory populations. Revealed Mef2c and Rora motifs enriched in PV interneurons (p < 10^-22 and p < 10^-9).
Model System: Mouse visual cortex: SMART-seq2 scRNA-seq (14,249 cells) and scATAC-seq gene activity matrix from prefrontal cortex
Statistical Significance: p < 10^-22 for Mef2c motif enrichment, p < 10^-9 for Rora
BANKSY delineated granular layer, Purkinje neurons, and MLIs more accurately than nonspatial clustering. Identified 8 clusters in Slide-seq v.2 corresponding to cell types vs 6 from nonspatial clustering. BANKSY yielded lower NCC scores confirming more contiguous clusters.
Model System: Mouse cerebellum Slide-seq v.1 and v.2 datasets
Statistical Significance: r=0.85 (BANKSY) vs r=0.44 (nonspatial) correlation with RCTD weights for granular layer
BANKSY separated CA3 neurons from SSC neurons and fornix from thalamic oligodendrocytes. Nonspatial and MERINGUE merged these subtypes. BANKSY identified region-specific cell types with subtly distinct transcriptomes. Validated with scRNA-seq using DEGs and guilt-by-association genes.
Model System: Mouse hippocampus VeraFISH data
Statistical Significance: Multiple comparisons across clustering resolutions (16-20 clusters)
Revealed role of astrocytes and microglia in unfolded protein response and cytokine signalling. CD4+ CTLs more prevalent with increased interferon-gamma response. Endothelial cells especially sensitive to IFNG.
Model System: Human midbrain specimens from PD patients and healthy individuals
Statistical Significance: Not applicable
Awuah Wireko Andrew et al., (2023)
Uncovered disease-specific gene expression changes and disrupted cellular pathways. Found high cytotoxic T cells, lower monocytes in ALS CSF. Identified novel CD8+ T-cell subtypes with varied stemness gene expression.
Model System: ALS patient-derived motor neurons, CSF samples
Statistical Significance: Not applicable
Awuah Wireko Andrew et al., (2023)
Identified 461 clusters and 3313 subclusters organized by developmental origins. Found unexpectedly high diversity of midbrain and hindbrain neurons (splatter neurons). Area-specific cortical neurons identified. Astrocytes exhibited regional diversity at multiple scales with telencephalon-specific and location-specific subtypes. Oligodendrocyte precursors comprised two distinct major types: Type 1 (telencephalon-specific) and Type 2 (non-telencephalon).
Model System: Human postmortem brain tissue from 3 donors (18-68 years, no neuropsychiatric conditions)
Statistical Significance: N/A - descriptive study
Confirmed RNA-seq findings spatially. Dopaminergic cells demarcated PBP, SN, and VTA. GABAergic cells distinguished SN pars compacta vs reticulata. Glutamatergic PVALB+ cells occupied red and pontine nuclei. Noradrenergic cells marked locus coeruleus. Spatial distributions matched RNA-seq clusters for lower rhombic lip neurons and CALB2+ dopaminergic cells. Revealed combinatorial neuropeptide and neurotransmitter expression patterns.
Model System: Fresh-frozen human postmortem brain tissue sections from midbrain and hindbrain regions
Statistical Significance: N/A
Validated presence of OTX2+, SOX14+, and CASR+ cells (midbrain-derived inhibitory neurons) in the efferent nuclei of the pons (PnEN). Confirmed localization of these marker genes in pontine regions.
Model System: Fresh-frozen human postmortem brain tissue from pons region
Statistical Significance: N/A
Identified 14 TH+ subtypes (vs 10 in Kamath et al.). Found 7 new TH+ subtypes including SOX6 LPL subtype in substantia nigra and 4 CALB1+ subtypes in periaqueductal grey and VTA. Identified third class of TH+ neurons co-expressing GABAergic markers (CALCR and EBF2 clusters).
Model System: Human midbrain dopaminergic neurons from this study vs published dataset
Statistical Significance: Cross-validation performed with varying parameters
EMBER distinctly discriminated tau deposits localized to neurons, astrocytes, and oligodendrocytes in PiD; neurons, astrocytes, and oligodendrocytes have distinct conformational strains in same brain; spatial resolution revealed cell-type specific strain variation
Model System: Pick's disease brain sections with tau inclusions in neurons, astrocytes, and oligodendrocytes
Statistical Significance: Cell-type specific cluster separation
Microglia expressed highest TLR5 levels; adult microglia expressed higher TLR5 than neonatal microglia; astrocytes and Oli-neu cells expressed low TLR5; TLR5 was barely detectable in cortical neurons
Model System: Primary neonatal microglia, adult microglia, astrocytes, and cortical neurons from C57BL/6 mice; Oli-neu oligodendroglial precursor cell line
Statistical Significance: P<0.05; P<0.01
TLR5 protein readily detectable in microglia and astrocytes (to lesser extent); not detected in cortical neurons; antibody specificity confirmed in Tlr5-/- mice
Model System: Cultured neonatal microglia, astrocytes, and neurons from C57BL/6 (WT) and Tlr5-/- mice
Flagellin induced neuronal loss in dose and time-dependent manner; 10ng/ml caused 19.2% loss (P=0.017); 100ng/ml caused 30.9% loss (P=0.0042) after 72h; neurons co-cultured with Tlr5-/- microglia protected; flagellin did not affect neurons in absence of microglia
Model System: Co-cultures of cortical neurons and microglia from WT or Tlr5-/- mice (ratio 8:1)
Statistical Significance: P<0.05; P<0.01 vs control
97% of cortical neurons express at least one NPP gene; 80% express at least one NPP at >1,000 CPM. Npy, Sst, Vip, and Tac2 rank as top 4 by pFPKM. Eleven of 18 NPP genes rank in top percentile of all protein-coding genes.
Model System: Mouse cortical neurons from primary visual cortex (VISp) and anterior lateral motor cortex (ALM)
Statistical Significance: N/A
Stephen J Smith et al., (2019)
98% of neurons express at least one NP-GPCR gene; 78% express at least one at >100 CPM. Most NP-GPCR genes expressed well above median for all protein-coding genes.
Model System: Mouse cortical neurons from VISp and ALM
Statistical Significance: N/A
Stephen J Smith et al., (2019)
47 NP genes achieve average RI = 0.925 for neuron type classification; 62% of neurons classified correctly at type level. This significantly exceeds random gene subsets (RI = 0.641 +/- 0.047) and expression-matched random subsets (RI = 0.843 +/- 0.027).
Model System: Mouse cortical neurons - 115 transcriptomic types from Tasic 2018 dataset
Statistical Significance: p<0.01 (bootstrap)
Stephen J Smith et al., (2019)
Modal number of co-expressed NPP genes is 2-5 per neuron; modal number of co-expressed NP-GPCR genes is 6. Multiple cognate NPP/NP-GPCR pairs commonly co-expressed in same neuron, suggesting possible autocrine signaling.
Model System: Mouse cortical neurons
Statistical Significance: N/A
Stephen J Smith et al., (2019)
Transcriptional changes strongest and highly cell-type-specific early in disease. Generalized activation of proteostasis and stress response genes in advanced disease. Sex-biased gene expression patterns in neurons and oligodendrocytes. Myelination-related processes recurrently altered across cell types.
Model System: Human postmortem prefrontal cortex
Statistical Significance: Not specified
Cláudio Gouveia Roque et al., (2024)
AD neurons accumulate 874 more somatic single-nucleotide variants on average than control cells (49% increase). Cytosine-to-adenine substitutions enriched in AD neurons, associated with oxidative damage. Base excision repair impaired in AD.
Model System: Human AD postmortem brain neurons
Statistical Significance: Not specified
Cláudio Gouveia Roque et al., (2024)
Cell-level overdispersion decreased with increasing gene expression. Subject-level overdispersion was largely attributed to subject-level covariates (age, sex, AD status). Cell-level overdispersion resulted from subpopulation heterogeneity. ~90% and ~80% of genes analyzed using NEBULA-LN alone in excitatory neurons (CPS~700) and oligodendrocytes (CPS~380).
Model System: Human postmortem brain tissue - 48 subjects from ROSMAP cohort
Statistical Significance: N/A - descriptive analysis
Successfully annotated snmC-seq profiles with high confidence using Allen Brain Atlas reference. RNA-assisted annotation provided clearer labels than unsupervised clustering (e.g., L6 neurons correctly labeled as near-projecting vs deep neocortical laminar 6b).
Model System: Human cortex snmC-seq dataset
Statistical Significance: Not applicable
85-90% of most predictive molecular pathways in brain were also top predictors in blood. Common pathways: blood coagulation, angiogenesis, p53, B cell activation, Wnt signaling. Brain cell types: astrocytes (38% ROSMAP, 22% HBTRC), microglia (4% ROSMAP, 48% HBTRC), oligodendrocyte precursor cells (35% ROSMAP, 17% HBTRC), neurons, endothelial cells.
Model System: ROSMAP and HBTRC brain tissues, ADNI blood
Statistical Significance: Not applicable (enrichment analysis)
T807 perfectly colocalized with tau-containing neurons and dystrophic neurites. Confirmed strong T807 binding to tau pathology in AD but not to cerebral amyloid, DLB, MSA, or TDP-43. Tangles and dystrophic neurites account for most of the in vivo T807 signal.
Model System: Human AD brain tissue
Statistical Significance: N/A
Hartmuth C. Kolb, José Ignacio Andrés (2017)
Most glutamatergic cell types shared among multiple areas with continuous gradients. Medial (RSP/ACA) and lateral (TEa-PERI-ECT) regions most distinct. Anterior-posterior transitions more continuous. IT neurons continuously distributed across cortical depth (L2/3 to L6).
Model System: Mouse isocortex - multiple cortical areas
Statistical Significance: N/A
Aβ molecular associates enriched in pyramidal cells (q=0.002, δ=3.804) and endothelial-mural cells (q=0.008, δ=2.950); tau associates enriched in interneurons (q=0.021, δ=2.834); Aβ∙tau signature highly enriched in microglia (q<0.001, δ=10.425)
Model System: Gene sets from transcriptomic analysis with single-cell data from mouse somatosensory cortex and hippocampus CA1
Statistical Significance: q < 0.05
Sanchez-Rodriguez et al., (2023)
Excitatory neurons had most eGenes (7,331), followed by inhibitory neurons (2,214), oligodendrocytes (1,968), astrocytes (1,705), OPCs (1,284), microglia (899), and endothelial cells (532). 46% of eGenes (4,598) were cell type-specific.
Model System: Human DLPFC - seven cell types: excitatory neurons, inhibitory neurons, astrocytes, microglia, oligodendrocytes, OPCs, endothelial cells
Statistical Significance: FDR < 0.05
234 of 6,414 (3.6%) eGenes replicated in iPSC-derived neurons; 121 of 2,529 (4.8%) replicated in astrocytes. Most eQTLs had same direction in vivo and in vitro. Exception: MAPT gene showed opposite direction of effect in iPSC-derived vs brain tissue.
Model System: iPSC-derived excitatory neurons and astrocytes from ROS/MAP participants
Statistical Significance: P<1x10-6 for replication above chance
11 PD risk loci colocalized with 13 eGenes. Excitatory neurons achieved the largest number of colocalized loci.
Model System: Human DLPFC cell types
Statistical Significance: PP.H4 > 0.8
57 SCZ loci colocalized with 75 eGenes. Excitatory neurons had largest number of colocalized loci.
Model System: Human DLPFC cell types
Statistical Significance: PP.H4 > 0.8
Most SCN neurons exhibit robust cell-autonomous limit cycle oscillations. Central SCN neurons show higher robustness (V approx 1) while surrounding tissues show noise-induced oscillations (V approx 0). Parameters Hill coefficient (n=3-8) and delay dispersion (2-5 hours) determine oscillator phenotype. Mean delay times for Cry1 oscillators estimated at 8-10 hours.
Model System: Organotypic mouse SCN slices expressing CRY1-LUC (three biological replicates)
Statistical Significance: Kolmogorov-Smirnov test with Bonferroni correction: 99.84% of locations accepted Gaussianity of residuals
LC neuronal loss averages 63% in AD; LC volume decreases by 8.4% per Braak stage increase; 8% of LC neurons are p-tau-positive at Braak stage 0, doubling by Braak stage I, reaching 100% by Braak stage VI; rostral portion affected more severely (83% loss) compared to middle (23%) and caudal (15%) parts
Model System: Human postmortem brain tissue
Statistical Significance: Significant correlation between LC volume loss and Braak stage (p<0.05)