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. 2015 Jul;10(7):1023-5.
doi: 10.4103/1673-5374.160059.

Glycogen and amyloid-beta: key players in the shift from neuronal hyperactivity to hypoactivity observed in Alzheimer's disease?

Britanny Bass  1 , Sarah Upson  1 , Kamolika Roy  1 , Emily L Montgomery  1 , Tuula O Jalonen  1 , Ian V J Murray  1
Affiliations

Glycogen and amyloid-beta: key players in the shift from neuronal hyperactivity to hypoactivity observed in Alzheimer's disease?

Britanny Bass et al. Neural Regen Res. 2015 Jul.
No abstract available

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Figures

Figure 1
Figure 1
Depiction of changes in astrocytes, neurons and blood vessels in the hyper- and hypoactive states in Alzheimer's disease (AD). Hyperactive state: Increased neuronal activity results in the synaptic release of amyloid-beta (Aβ) and glutamate, with Aβ (pM levels) feedback to further increase synaptic activity. Neuronal activity (e.g., glutamate ◇) stimulates the astrocytes and results in several changes in the astrocyte and their glycogen concentration. For example, increased levels of calcium lead to increased glycogenolysis, glucose uptake and vasoactive substance release by the astrocyte end-feet surrounding blood vessels. Homeostatic mechanisms, such as elevated levels of Aβ (nM) and adenosine A2A re-ceptors (A2A) exist to reduce neuronal hyperactivity. A pathological hyperactive state occurs early on in AD progression, during the stage of mild cognitive impairment (MCI). It is likely that dysregulation of the homeostatic mechanisms of Aβ and A2A, along with depleted glycogen reserves lead to subsequent hypoactivity. Hypoactive state: This state occurs later in AD, and we speculate it to be the result of chronic hyperactivity. For example, it is known that the combination of increased synaptic secretion and reduced clearance of Aβ result in the misfolding and polymerization of Aβ, which accumulate as amyloid plaques (multiple □). These plaques serve as a reservoir of oligomeric Aβ (dimer □). The elevated levels of Aβ (nM) inhibit synaptic activity and result in neuronal death (death depicted by dotted lines). Astrocytes also become activated (depicted by star shape), but this is not discussed in the text. In AD, cerebrospinal fluid (CSF) Adenosine triphosphate (ATP) levels (Coskuner and Murray, 2014), brain glucose utilization, and blood flow are all decreased (reviewed by Murray et al., 2011), while A2A levels are upregulated (Gomes et al., 2011). Although glycogen levels have not been measured in AD, based on reasons given in the text, we predict that glycogen levels will be low. Thus we have linked Aβ, glycogen, and A2A levels to the progression of hyperactivity to hypoactivity. ◇ Glutamate; ⌂ Glucose transporter; ◼ vasoactive sub-stances; □ amyloid beta (Aβ) - monomer, oligomer and fibril (shown as dimers and multimers respectively); ○ glucose.
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