Substantia Nigra Lesions in Alzheimer Disease and Normal Aging

Kazee, Ann Marie; Cox, Christopher; Richfield, Eric K.

doi:10.1097/00002093-199509020-00001

Cited by 47 publications

(29 citation statements)

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“…However, in contrast to PD, tremor is rare [128]. EPS signs increase in prevalence as AD advances and correlated with tau accumulation and dopaminergic neuronal loss [125,126]. EPS signs often parallel neuropsychiatric symptoms including depression, hallucination and cognitive decline, possibly reflecting deficiency of dopamine neurotransmission.…”

Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

“…Neuropathological studies confirmed SN susceptibility to NFTs and neurodegeneration in AD, but severe cell loss is rarely present in this nucleus in contrast to the rest of the IC [16,124,125,127,130]. On the other hand, in pre-immunohistochemistry era studies, AD cases with SN pathology are often misclassified as having PD and are excluded from the analysis, leading to an underestimation of SN involvement in AD pathology [125].…”

Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

“…On the other hand, in pre-immunohistochemistry era studies, AD cases with SN pathology are often misclassified as having PD and are excluded from the analysis, leading to an underestimation of SN involvement in AD pathology [125]. Another confounder in SN analysis in AD is that neuromelanin may obscure visualization of intraneuronal NFTs and initial lesions could be easily overlooked [131].…”

Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

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Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Theofilas

Dunlop

Heinsen

et al. 2015

JAD

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Pharmacological interventions in Alzheimer's disease (AD) are likely to be more efficacious if administered early in the course of the disease, foregoing the spread of irreversible changes in the brain. Research findings underline an early vulnerability of the isodendritic core (IC) network to AD neurofibrillary lesions. The IC constitutes a phylogenetically conserved subcortical system including the locus coeruleus in pons, dorsal raphe nucleus and substantia nigra in the midbrain, and nucleus basalis of Meynert in basal forebrain. Through their ascending projections to the cortex, the IC neurons regulate homeostasis and behavior by synthesizing aminergic and cholinergic neurotransmitters. Here we reviewed the evidence demonstrating that neurons of the IC system show neurofibrillary tangles in the earliest stages of AD, prior to cortical pathology, and how this involvement may explain pre-amnestic symptoms, including depression, agitation and sleep disturbances in AD patients. In fact, clinical and animal studies show a significant reduction of AD cognitive and behavioral symptoms following replenishment of neurotransmitters associated with the IC network. Therefore, the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in AD.

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Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

Section: Substantia Nigra and The Dopaminergic Systemmentioning

confidence: 99%

See 1 more Smart Citation

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Theofilas

Dunlop

Heinsen

et al. 2015

JAD

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“…We did not examine whether extrapyramidal signs, which may be associated with neuronal loss and Lewy bodies in the substantia nigra [17,27,28], were associated with ApoE Â4. We excluded subjects with Lewy bodies at autopsy, who would be expected to exhibit these clinical Mean values are shown with standard deviations in parentheses, except for sex, where actual numbers are shown.…”

Section: Discussionmentioning

confidence: 99%

“…Although we cannot exclude the possibility that an occasional Lewy body might have been present in sections that were not examined, our subjects met clinical and pathologic criteria for typical AD. Substantia nigra cell loss is associated with typical AD [17].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E ε4 Is Associated with Neuronal Loss in the Substantia nigra in Alzheimer’s Disease

Camicioli¹,

Kaye²,

Payami³

et al. 1999

Dement Geriatr Cogn Disord

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Apolipoprotein E ε4 (ApoE ε4) is associated with an earlier age at onset of Alzheimer’s (AD) and possibly Parkinson’s disease, suggesting a general role for ApoE ε4 in neuronal plasticity. Among 31 prospectively assessed subjects with pathologically confirmed AD (without Lewy bodies), ε4+ subjects had a longer duration of disease (by 2.8 years, p = 0.04). Only cell loss in the substantia nigra (p = 0.002) was associated with ε4. Neither neurofibrillary tangles nor plaque counts were associated with ε4. Cell counts of pigmented neurons in single midbrain sections in ε4+ specimens were 72% of those in ε4– substantia nigra (p = 0.04). These findings confirm that cell loss in the substantia nigra is associated with ε4 in AD.

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Initial results of a genome survey for novel alzheimer's disease risk genes: association with a locus on the X chromosome

et al. 1998

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As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45+/-S.E. 0.06) than controls (0.22+/-S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29+/-S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.

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Substantia Nigra Lesions in Alzheimer Disease and Normal Aging

Cited by 47 publications

References 0 publications

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Apolipoprotein E ε4 Is Associated with Neuronal Loss in the Substantia nigra in Alzheimer’s Disease

Initial results of a genome survey for novel alzheimer's disease risk genes: association with a locus on the X chromosome

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