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Efforts in AD drug development have largely focused on treating neuronal pathologies that appear relatively late in the disease. The neuroenergetic hypothesis, however, focuses on the early event of glucose hypometabolism in AD, where astrocytes play a key role, caused by an imbalanced neuron-astrocyte lactate shuttle. This further results in a state of oxidative stress and neuroinflammation, thereby compromising the integrity of astrocyte-neuron interaction. Compromised astrocytic energetics also enhance amyloid generation, further increasing the severity of the disease. Additionally, apolipoprotein E (APOE), the major genetic risk factor for AD, is predominantly secreted by astrocytes and plays a critical role in amyloid clearance and regulates glucose metabolism in an amyloid-independent manner. Thus, boosting the neuroprotective properties of astrocytes has potential applications in delaying the onset and progression of AD. This review explores how the metabolic dysfunction arising from astrocytes acts as a trigger for the development of AD.<\/jats:p>","DOI":"10.1515\/hsz-2019-0140","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T05:03:07Z","timestamp":1560315787000},"page":"1113-1127","source":"Crossref","is-referenced-by-count":42,"title":["Contribution of astrocytes to metabolic dysfunction in the Alzheimer\u2019s disease brain"],"prefix":"10.1515","volume":"400","author":[{"given":"Shadaan","family":"Zulfiqar","sequence":"first","affiliation":[{"name":"Institute for Pharmacology and Clinical Pharmacy , Philipps University , Karl-von-Frisch Strasse , Marburg D-35043 , Germany"},{"name":"Marburg Center for Mind, Brain and Behavior , Philipps University , Marburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pretty","family":"Garg","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology and Clinical Pharmacy , Philipps University , Karl-von-Frisch Strasse , Marburg D-35043 , Germany"},{"name":"Marburg Center for Mind, Brain and Behavior , Philipps University , Marburg , Germany"},{"name":"Institute for Neuro and Sensory Physiology , Heinrich Heine University , D\u00fcsseldorf D-40225 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Nieweg","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology and Clinical Pharmacy , Philipps University , Karl-von-Frisch Strasse , Marburg D-35043 , Germany"},{"name":"Marburg Center for Mind, Brain and Behavior , Philipps University , Marburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"2026041717065351731_j_hsz-2019-0140_ref_001_w2aab3b7c44b1b6b1ab2ab1Aa","doi-asserted-by":"crossref","unstructured":"Akama, K.T. and Van Eldik, L.J. 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