Monoaminergic Neuropathology in Alzheimer's disease

Goran Šimić, Mirjana Babić Leko, Selina Wray, Charles R. Harrington, Ivana Delalle, Nataša Jovanov-Milošević, Danira Bažadona, Luc Buée, Rohan de Silva, Giuseppe Di Giovanni, Claude M. Wischik, Patrick R. Hof

Research output: Contribution to journalArticle

47 Citations (Scopus)
8 Downloads (Pure)

Abstract

None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.
Original languageEnglish
Pages (from-to)101-138
Number of pages38
JournalProgress in Neurobiology
Volume151
Early online date12 Apr 2016
DOIs
Publication statusPublished - Apr 2017

Fingerprint

Alzheimer Disease
tau Proteins
Locus Coeruleus
Neuropathology
Behavioral Symptoms
Neurobehavioral Manifestations
Penetrance
Apolipoproteins E
Amyloid
Epigenomics
Cerebral Cortex
Brain Stem
Neurons
Genes

Keywords

  • 5-hydroxytryptamine (serotonin)
  • Alzheimer's disease
  • amyloid beta (Aβ) peptide
  • blood-brain barrier
  • cerebrospinal fluid
  • epigenetics
  • locus coeruleus
  • metals
  • monoamines
  • neurofibrillary degeneration
  • non-cognitive symptoms
  • nucleus raphe dorsalis
  • phosphorylation
  • sleep-wake cycle
  • tau protein

Cite this

Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Jovanov-Milošević, N., ... Hof, P. R. (2017). Monoaminergic Neuropathology in Alzheimer's disease. Progress in Neurobiology, 151, 101-138. https://doi.org/10.1016/j.pneurobio.2016.04.001

Monoaminergic Neuropathology in Alzheimer's disease. / Šimić, Goran; Leko, Mirjana Babić; Wray, Selina; Harrington, Charles R.; Delalle, Ivana; Jovanov-Milošević, Nataša; Bažadona, Danira; Buée, Luc; Silva, Rohan de; Giovanni, Giuseppe Di; Wischik, Claude M.; Hof, Patrick R.

In: Progress in Neurobiology, Vol. 151, 04.2017, p. 101-138.

Research output: Contribution to journalArticle

Šimić, G, Leko, MB, Wray, S, Harrington, CR, Delalle, I, Jovanov-Milošević, N, Bažadona, D, Buée, L, Silva, RD, Giovanni, GD, Wischik, CM & Hof, PR 2017, 'Monoaminergic Neuropathology in Alzheimer's disease', Progress in Neurobiology, vol. 151, pp. 101-138. https://doi.org/10.1016/j.pneurobio.2016.04.001
Šimić G, Leko MB, Wray S, Harrington CR, Delalle I, Jovanov-Milošević N et al. Monoaminergic Neuropathology in Alzheimer's disease. Progress in Neurobiology. 2017 Apr;151:101-138. https://doi.org/10.1016/j.pneurobio.2016.04.001
Šimić, Goran ; Leko, Mirjana Babić ; Wray, Selina ; Harrington, Charles R. ; Delalle, Ivana ; Jovanov-Milošević, Nataša ; Bažadona, Danira ; Buée, Luc ; Silva, Rohan de ; Giovanni, Giuseppe Di ; Wischik, Claude M. ; Hof, Patrick R. / Monoaminergic Neuropathology in Alzheimer's disease. In: Progress in Neurobiology. 2017 ; Vol. 151. pp. 101-138.
@article{8177319c1ac349d6a9703681589d2b6a,
title = "Monoaminergic Neuropathology in Alzheimer's disease",
abstract = "None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.",
keywords = "5-hydroxytryptamine (serotonin), Alzheimer's disease, amyloid beta (Aβ) peptide, blood-brain barrier , cerebrospinal fluid, epigenetics, locus coeruleus, metals, monoamines, neurofibrillary degeneration, non-cognitive symptoms, nucleus raphe dorsalis, phosphorylation, sleep-wake cycle, tau protein",
author = "Goran Šimić and Leko, {Mirjana Babić} and Selina Wray and Harrington, {Charles R.} and Ivana Delalle and Nataša Jovanov-Milošević and Danira Bažadona and Luc Bu{\'e}e and Silva, {Rohan de} and Giovanni, {Giuseppe Di} and Wischik, {Claude M.} and Hof, {Patrick R.}",
note = "Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.",
year = "2017",
month = "4",
doi = "10.1016/j.pneurobio.2016.04.001",
language = "English",
volume = "151",
pages = "101--138",
journal = "Progress in Neurobiology",
issn = "0301-0082",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Monoaminergic Neuropathology in Alzheimer's disease

AU - Šimić, Goran

AU - Leko, Mirjana Babić

AU - Wray, Selina

AU - Harrington, Charles R.

AU - Delalle, Ivana

AU - Jovanov-Milošević, Nataša

AU - Bažadona, Danira

AU - Buée, Luc

AU - Silva, Rohan de

AU - Giovanni, Giuseppe Di

AU - Wischik, Claude M.

AU - Hof, Patrick R.

N1 - Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.

PY - 2017/4

Y1 - 2017/4

N2 - None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

AB - None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

KW - 5-hydroxytryptamine (serotonin)

KW - Alzheimer's disease

KW - amyloid beta (Aβ) peptide

KW - blood-brain barrier

KW - cerebrospinal fluid

KW - epigenetics

KW - locus coeruleus

KW - metals

KW - monoamines

KW - neurofibrillary degeneration

KW - non-cognitive symptoms

KW - nucleus raphe dorsalis

KW - phosphorylation

KW - sleep-wake cycle

KW - tau protein

U2 - 10.1016/j.pneurobio.2016.04.001

DO - 10.1016/j.pneurobio.2016.04.001

M3 - Article

VL - 151

SP - 101

EP - 138

JO - Progress in Neurobiology

JF - Progress in Neurobiology

SN - 0301-0082

ER -