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Altered Cholesterol Metabolism in Alzheimer's Disease Development


Altered Cholesterol Metabolism in Alzheimer's Disease Development


Academic year 2023/2024

Paola Francesca Gamba (Titolare del corso)
Gabriella Marisa Leonarduzzi (Titolare del corso)
Gabriella Testa (Assistente)
Erica Staurenghi (Assistente)
Serena Giannelli (Assistente)
Degree course
2nd year
Teaching period
Course disciplinary sector (SSD)
MED/04 - experimental medicine and pathophysiology

Sommario del corso


Course objectives

It is well documented that altered cholesterol metabolism in the brain and hypercholesterolemia, together with oxidative stress and neuroinflammation, significantly contribute to Alzheimer’s disease (AD) pathogenesis. Among AD brain hallmarks, the presence of reactive astrocytes correlates with neuronal loss and cognitive deficits. Evidence indeed supports the role of reactive astrocytes as mediators of changes in neurons, including synapses.

Cholesterol oxidation products, known as oxysterols, are potentially involved in the pathogenesis of major chronic human diseases, including AD. The analysis of oxysterols in plasma and brain may contribute to clarify the role of cholesterol metabolism in AD pathogenesis and the crosstalk between astrocytes and neurons; moreover, it may be helpful in developing therapeutic strategies to prevent or slow its development. The deepening of the experimental modelling of the disease is also crucial to understanding how the current disease models can be applied to gain useful results while also considering their limitations. These systems are important for gaining a greater understanding of the cause and progression of AD and for testing potential therapeutics to advance drug development.


Results of learning outcomes

The aim of these activities is to offer PhD students in Experimental Medicine and Therapy (second year – 38° cycle) an up-date on current knowledge about cholesterol homeostasis and the involvement of cholesterol oxidation products in the pathogenesis of AD, with a technical insight into the experimental models employed and the current therapies.



The activity will be structured in 3 lessons:

First lesson: 1) Alzheimer’s disease pathogenesis; 2) Current experimental models employed for the study of Alzheimer’s disease (Dr Serena Giannelli) - 3 hours (lesson+ test)

Second lesson: 1) Cholesterol metabolism in the healthy and AD brain;  2) Therapeutic strategies against Alzheimer’s disease (Dr Gabriella Testa) - 3 hours (lesson + test)

Third lesson: 1) Role of astrocyte reactivity in Alzheimer’s disease progression; 2) Experimental therapeutic strategies targeting ApoE and astrocyte reactivity (Dr Erica Staurenghi) –3 hours (lesson + test)


Learning assessment methods

After each lesson, the evaluation will consist of a written test in presence: 1 open-ended question and 4 multiple choice questions (5 answers, without penalty for wrong answer).
The understanding of the topics covered will be assessed. The evaluation will be expressed in eligibility.

Suggested readings and bibliography



  1. Gamba P, Giannelli S, Staurenghi E, Testa G, Sottero B, Biasi F, Poli G, Leonarduzzi G. The controversial role of 24-S-hydroxycholesterol in Alzheimer’s disease. Antioxidants 2021, 10:740.
  2. Gamba P, Staurenghi E, Testa G, Giannelli S, Sottero B, Leonarduzzi G. A Crosstalk Between Brain Cholesterol Oxidation and Glucose Metabolism in Alzheimer's Disease. Front Neurosci. 2019, 13:556.
  3. Sottero B, Leonarduzzi G, Testa G, Gargiulo S, Poli G, Biasi F. Lipid oxidation derived aldehydes and oxysterols between health and disease. Eur J Lipid Sci Technol. 2018: 1-16.
  4. Gamba P, Testa G, Gargiulo S, Staurenghi E, Poli G, Leonarduzzi G. Oxidized cholesterol as the driving force behind the development of Alzheimer's disease. Front Aging Neurosci. 2015, 7:119.
  5. Staurenghi E, Giannelli S, Testa G, Sottero B, Leonarduzzi G, Gamba P. Cholesterol Dysmetabolism in Alzheimer's Disease: A Starring Role for Astrocytes? Antioxidants (Basel). 2021 Nov 26;10(12):1890.



Courses strongly recommended for the second year:

May 17, 2024 14:00 -17:00

May 24, 2024 14:00 -17:00

May 31, 2024 14:00 -17:00

  • Closed
    Enrollment opening date
    15/11/2023 at 12:00
    Enrollment closing date
    13/05/2024 at 12:00
    Last update: 13/05/2024 12:17
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