Review articleMonoaminergic neuropathology in Alzheimer’s disease
Section snippets
Clinical and neuropathological criteria for AD diagnosis
Alzheimer’s disease (AD) accounts for 60–70% of cases of dementia (World Health Organization, WHO Fact Sheet No. 362, March 2015). The report of Alzheimer’s Disease International (ADI, The World Alzheimer Report, 2015) showed that nearly 35.6 million people suffered from dementia in 2012. It is estimated that this number will quadruple by 2050. Therefore, the WHO in 2012 declared AD a global public health priority. There is still no effective treatment to prevent or cure AD. Currently, approved
Serotonergic system
The impairment of serotonergic system in AD was shown in humans both in vivo and postmortem. Early non-cognitive behavioral and psychological symptoms of dementia (BPSD), such as disturbances in mood, emotion expression and recognition (Waanders-Oude Elferink et al., 2015), appetite, sleep-wake cycle, confusion, agitation, and depression are probably clinical signs of serotonergic nuclei involvement in AD (Šimić et al., 2009). One of them, sundowning (the increase in one or more abnormal
Alterations of the serotonergic system in AD
Similarly to NIA/AA guidelines, the current clinical criteria for diagnosis of AD of the American Psychiatric Association (DSM-5) are mostly focused on cognitive deficits produced by the dysfunction of hippocampal and association neocortical areas. These changes are neuropsychologically scored as number of points that, in the most commonly used Mini-Mental State Examination (MMSE), ranges from 0 to 30 points, where 30 reflects normal mental status across many cognitive domains (Folstein et al.,
Conclusions
Pathological changes in monoaminergic nuclei, particularly the noradrenergic LC and serotonergic DRN, but also dopaminergic, histaminergic, and melatonergic nuclei and pathways, observed during the early course of AD probably have a profound influence not only on the complex symptoms and pathogenesis in AD, but also in other primary and secondary tauopathies, especially FTD (Boban et al., 2010). The link between depression and AD, depression being a frequent preclinical manifestation of AD, is
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
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