Table 1.

In vivo studies related to neurotransmission in AD. Abbreviations: 5 HT, 5-hydroxy-tryptamine, Serotonin; ACh, Acetylcholine; AChE, Acetylcholinesterase; APPswe, Amyloid-beta precursor protein with Swedish mutation; Aβ, Amyloid-beta; AβO, Amyloid-beta oligomers; AβPP, Amyloid-beta precursor protein; ChAT, Choline acetyltransferase; DA, Dopamine; DAergic, Dopaminergic; GABA, Gamma-aminobutyric acid; MAergic, Monoaminergic; mGlu2, Metabotropic glutamate receptor 2; NA, Noradrenergic; NMDAR, N-methyl-D-aspartate receptor; PS, presenilin transgenic; SN, Substantia nigra; TH-, Tyrosine hydroxylase negative; TH+, Tyrosine hydroxylase positive; VTA, Ventral tegmental area.

Animal Model.	Gender	Age	Pathology Involved	Neurotransmission Dysfunction	Behavioral Effects	References
APPswe/PS1dE9 mice	N/A	4–18 months old	Degeneration and loss of forebrain 5-HT and NA axons after Aβ deposits	Monoaminergic neurodegeneration	Anxiety-related behaviors in 18 months	[57]
Swiss mice treated with AβO	N/A	3 months old	Development of Aβ plaques	AβO disrupts 5-HT homeostasis	Depressive-like behavior	[58]
APPswe/PS1dE9 mice	Male	4, 8, 11 months old	Progressive accumulation of Aβ protein.	Significant decrease in 5-HT2A receptor binding	Memory impairment	[59]
5xFAD mice	Male	6 months old	Significant decrease of both TH+ and TH- cells in DA-producing areas	SN-VTA networks are enhanced to the synchronization of neuronal firing activity in DA-producing nuclei	Cognitive malfunction Synaptic malfunction	[65]
Tg2576 mice	Male	2 and 6 months old	Degeneration of VTA DAergic neurons	Reduced noradrenergic transmission in dorsal subiculum	Age-related impairment of memory and non-cognitive functions	[66]
Tg2576 mice	N/A	4–6 and 9–11 months old	Aβ were prominent in 20-month-old mice	Reduced ACh release from hippocampus in 9- to 11-month-old mice	Memory impairment present in 9- to 11-month-old mice	[30]
APP/PS1 mice	N/A	3 and 7 months old	Aβ plaques deposition after cholinergic degeneration	Dramatically reduced cholinergic neurons Neuronal loss in nucleus basalis	Early memory impairment Progressive impairment	[34]
APP/PS1 and 5xFAD mice	N/A	8 and 13 months old	Aβ plaques deposition and reactive astrocytes	Aberrant increase in GABA release from reactive astrocytes	Impaired learning and memory	[36]
AβPP/PS mice	Male	2–4 months old	Abnormal glutamate release precedes cognitive decline	Significantly increased potassium-evoked glutamate release in CA1	Cognitive decline	[51]
AβPPswe-PS1dE9 mice	N/A	6 months old	Deposition of Aβ plaques	Significant decrease in cortical glutamate and GABA Glucose, GABA and glutamate reduced in hippocampus and striatum	Impairment of cognitive function and memory	[37]
TgAPP23 mice	Male and female	24 months old	Deposition of Aβ plaques and cholinergic degeneration	Decreased ChAT-positive boutons in neocortex Significant reduction of ChAT-positive neurons volume in basal forebrain	N/A	[26]
PS2APP mice	Female	20 or 24 months old	Deposition of Aβ plaques	Significant reduction of glutamate level in frontal cortex	N/A	[52]
TgAPP23 mice	N/A	7–8 months old	Dysfunction of cholinergic and monoaminergic systems	Decreased AChE and ChAT activity in basal forebrain nuclei Increased 5-HT levels in parietal cortex and occipital cortex	N/A	[27]
PDAPP mice	Male and female	4–6 months old	Deposition of Aβ plaques	Reduced basal and evoked ACh release from hippocampus	Hyper-locomotor function	[33]
3xTg-AD mice	Male and female	2–4, 13–15 and 18–20 months old	Aβ plaques deposition with cholinergic degeneration and alteration of neurotrophic factors	Reduced ChAT in medial septum/vertical limb of the diagonal band of Broca in 18- to 20-month-old mice Decreased hippocampal ChAT activity in 13- to 15-month-old mice	N/A	[28]
hAPP-J20 mice	N/A	6 months old	Altered synaptic plasticity and cognitive function	Significantly decreased phospho GluN2B levels and hippocampal LTP	Impaired learning and memory	[42]
TgCRND8 mice	N/A	2 and 7 months old	Aβ plaques deposition, oxidative stress, reactive glial cells and neurodegeneration	Reduced ChAT-positive neurons and ACh levels.	Cognitive impairment	[31]
PS2APP mice	Male	5, 9, 13 and 17 months old	Deposition of Aβ plaques	Significant loss of mGlu2 receptors in entorhinal cortex and lacunosum moleculare regions	N/A	[53]
PS2APP mice	Male	3–4 months old	Altered synaptic plasticity	Aberrant GluN2B-NMDAR function	N/A	[54]
PDAPP mice	Male	2, 4, 12 and 24 months old	Aβ plaques deposition with cholinergic degeneration	Reduced Cholinergic nerve terminals density Significantly decreased ChAT activity	N/A	[32]
3xTg-AD mice	N/A	9–23 months old	Deposition of Aβ plaques	Reduced ChAT and AChE-positive neurons	N/A	[29]
TgCRND8 mice	Male	3 months old	Deposition of Aβ plaques and neuronal degeneration	Significantly increased GluN1 in neocortex, hippocampus and cerebellum. Significantly increased GluA2 in neocortex but decreased in hippocampus	Cognitive impairment	[55]
TgCRND8 mice	Male and female	2–3 and 12–13 months old	Deposition of Aβ plaques	Decreased glutamate in hippocampus, cortex, frontal cortex and midbrain Decreased GABA in hippocampus, cortex and midbrain	N/A	[38]
TgCRND8 mice	Male	3 months old	Dysfunction of dopaminergic system	Increased dopamine level in the neostriata and frontal cortices Decreased dopamine level in the hippocampus	Cognitive impairment	[64]