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Evaluation of Magnetic Resonance Imaging as a Biomarker in Alzheimer’s Disease

Leacky Muchene, Ziv Shkedy

Hasselt University, Belgium

Luc Bijnens, Nikolay Manyakov, Tom Van De Casteele, Tom Jacobs

Janssen Pharmaceutica, Belgium

Marleen Verhoye, Jelle Praet, Annemie Van der Linden

University of Antwerp, Belgium

Astrid Bottelbergs, Mark Schmidt

Janssen Pharmaceutica, Belgium

Darrel Pemberton

Janssen Pharmaceutica, Belgium


Alzheimer’s Disease

Alzheimer's disease (AD), the most common cause of dementia, is an irreversible age-related condition resulting in an increase in dependency on care providers for basic functioning. Clinical symptoms of sporadic AD manifest mostly in the elderly population (at least 65 years) and include progressive deterioration of specific cognitive functions such as memory, speech, motor skills and perception (McKhann et al., 1984). A proper diagnosis of AD suffers from the lack of diagnostic tools that can accurately distinguish AD from other causes of cognitive impairment especially at an early stage of the disease (Blennow, 2004; Chetelat and Baron, 2003; Galvin and Sadowsky, 2012). Moreover, AD results in multiple pathological changes in the brain, which do not manifest the same way in all patients. The most common AD-related pathological changes in the brain include amyloid-beta protein plague deposition (Masters et al., 1985; Hardy and Selkoe, 2002), neurofibrillary tangle (hy- perphosphorylated tau) formation, and neuro-degeneration (Hol et al., 2003; Serrano-Pozo et al., 2011). How these changes influence the progression of AD is unfortunately not clearly understood since the onset of clinical symptoms of AD occurs much later than the onset of the pathological changes associated with the disease (Agronin, M.E., 2007). Considering the fact that there is no known cure for AD, an early diagnosis of the disease would therefore be preferable in order to allow for the introduction of treatments that may delay the progression of the disease such as a lifestyle intervention or novel therapeutic management of the patients.

From a practical point of view, although the pathological markers of AD are indicative of the disease progression, they can only be measured cross- sectionally (once per patient). This is due to the fact that pathological his?tology staining involves post-mortem examination, whose acquisition comes too late from a diagnostic point of view (Perl, 2010). Thus, potential biomakers which can be easily acquired in clinical follow-up of patients would be of interest in early diagnosis of the disease (Hampel et al., 2009). One of the challenges in current AD research is the availability of a suitable animal model, fully representative for the disease pathology. On the other hand, the advantage of using an animal model exhibiting only one pathological indication of AD is that it enables us to study the influence of one aspect of the disease, without the interaction of other pathological indications. The existing animal models mainly target one or a few aspects of the disease (Duff and Sule- man, 2004). An animal model with over-expressed Amyloid Precursor Protein (APP) gene and Presenilin (PS) results in variants of mouse models such as the APP/PS1 mouse model that was used in this experiment (Gotz and Gotz, 2009).

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