Ascending monoaminergic systems alterations in Alzheimer's disease. Translating basic science into clinical care

Trillo, Ludwig; Das, Devsmita; Hsieh, Wayne; Medina, Brian; Moghadam, Sarah; Lin, Bill Yuchen; Do, Dang Van; Sanchez, Martha Millan; Miguel, Zurine De; Ashford, J. Wesson; Salehi, Ahmad

doi:10.1016/j.neubiorev.2013.05.008

Cited by 190 publications

(180 citation statements)

References 223 publications

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“…In AD central and peripheral 5-HT neurotransmission decreases,. and it is consistent with a loss of 5-HT neurons in the raphe nuclei and associated loss of cortical 5-HT projections [8]. The aim of our study is to analyse the possible role of the 5HT2A receptor His452Tyr polymorphism on memory profile in a clinical set of AD patients at illness onset and at follow-up.…”

Section: Introductionsupporting

confidence: 56%

“…Probably the effect of His452Tyr polymorphism is no more evident when the 5HT2A receptors decrease, as in aged and demented people. Furthermore the pathogenesis of the impairment of memory and cognition in AD is due to a complex mechanism involving different pathways and different neurotransmitters (such as dopaminergic, cholinergic and serotoninergic system) [8] Conclusion…”

Section: Rey's Auditory Verbal Learning Test (Immediate and 15-min Dementioning

confidence: 99%

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A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

Guglielmi

Bizzarro

Valenza

et al. 2015

International Journal of Neuroscience

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The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers ( n = 111) and non-carriers ( n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups ( p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.

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Section: Introductionsupporting

confidence: 56%

Section: Rey's Auditory Verbal Learning Test (Immediate and 15-min Dementioning

confidence: 99%

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

Guglielmi

Bizzarro

Valenza

et al. 2015

International Journal of Neuroscience

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“…Serotonergic and noradrenergic nuclei are located in the pons and project widely to the forebrain; dysfunction of these nuclei has the potential to impair cognition and emotion. 39,40 mTBI resulting from LFP also impaired spatial working memory. In contrast to ASR, impairment of spatial working memory was transient.…”

Section: Pang Et Almentioning

confidence: 93%

Long-Lasting Suppression of Acoustic Startle Response after Mild Traumatic Brain Injury

Pang

Sinha

Avcu

et al. 2015

Journal of Neurotrauma

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Acoustic startle response (ASR) is a defensive reflex that is largely ignored unless greatly exaggerated. ASR is suppressed after moderate and severe traumatic brain injury (TBI), but the effect of mild TBI (mTBI) on ASR has not been investigated. Because the neural circuitry for ASR resides in the pons in all mammals, ASR may be a good measure of brainstem function after mTBI. The present study assessed ASR in Sprague-Dawley rats after mTBI using lateral fluid percussion and compared these effects to those on spatial working memory. mTBI caused a profound, long-lasting suppression of ASR. Both probability of emitting a startle and startle amplitude were diminished. ASR suppression was observed as soon as 1 day after injury and remained suppressed for the duration of the study (21 days after injury). No indication of recovery was observed. mTBI also impaired spatial working memory. In contrast to the suppression of ASR, working memory impairment was transient; memory was impaired 1 and 7 days after injury, but recovered by 21 days. The long-lasting suppression of ASR suggests long-term dysfunction of brainstem neural circuits at a time when forebrain neural circuits responsible for spatial working memory have recovered. These results have important implications for return-to-activity decisions because recovery of cognitive impairments plays an important role in these decisions.

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“…In addition to the degeneration of cortical and hippocampal neurons, Alzheimer disease is associated with the early and progressive degeneration of monoaminer gic neurons. 15,16 For these reasons, the development of hybrid drugs that behave as dual inhibitors of both ChEs and MAO are being actively produced to treat Alzheimer disease symp toms and potentially slow the disease progression. [17][18][19] In this regard, we have conceived a compound coded ASS234 (see the structure in the Methods section), [20][21][22] that is a a multi potent AChE/MAO inhibitor with the ability to cross the blood-brain barrier and that shows antioxidant and neuro protective properties with inhibitory effects on Aβ aggrega tion.…”

Section: J Psychiatry Neurosci 2017;42(1)mentioning

confidence: 99%

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

Serrano

Herrero-Labrador

Futch

et al. 2017

JPN

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Ascending monoaminergic systems alterations in Alzheimer's disease. Translating basic science into clinical care

Cited by 190 publications

References 223 publications

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

Long-Lasting Suppression of Acoustic Startle Response after Mild Traumatic Brain Injury

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

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