Abstract
Clinical symptoms of Alzheimer’s Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2.5 months old and cognitive impairment in between 3- and 5-month-old mice. In this work, the effect of chronic Aβ-immunotherapy on behavioral and cognitive abilities was tested by monthly administering the antibody fragment scFv-h3D6 to 3xTg-AD female mice from 5 to 9 months of age. An untreated group was used as a reference, as well as to attain some information on the effect of training during the longitudinal study. Behavioral and psychological symptoms of dementia (BPSD)-like symptoms were already evident in 5-month-old mice, in the form of neophobia and anxious-like behavior. The exploratory activity decreased over the longitudinal study, not only for 3xTgAD mice but also for the corresponding non-transgenic mice (NTg). Learning abilities of 3xTg-AD mice were not seriously compromised but an impairment in long-term spatial memory was evident at 5 months of age. Interestingly, scFv-h3D6-treatment affected the cognitive impairment displayed by 5-month-old 3xTg-AD mice. It is worth noting that training also reduced cognitive impairment of 3xTg-AD mice over the longitudinal study, suggesting that to properly quantify the isolated therapeutic potential of any drug on cognition using this model it is convenient to perform a prompt, age-matched study rather than a longitudinal study. In addition, a combination of both training and Aβ-immunotherapy could constitute a possible approach to treat Alzheimer’s disease.
Highlights
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide [1]
Both PBS-treated non-transgenic mice (NTg) and 3xTg-AD mice exhibited similar performances at 5 months of age in most of the parameters analyzed in the CT (Figure 2, Table 1)
We previously demonstrated that scFv-h3D6 administration reduces total tau levels in 22-month-old 3xTg-AD females [47]
Summary
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide [1]. Accumulation of the amyloid-β (Aβ) peptide in the neural tissue, either because of its overproduction or impaired clearance [2], is considered a key factor in the progression of this neurodegenerative disorder [3,4]. Other age-related, protective or disease-promoting factors have been shown to be involved in the disease progression [5]. Clinical symptoms include both cognitive and behavioral alterations. The first consist mainly of memory loss and learning deficiencies, as well as impairments in other cognitive abilities interfering with mood, reason, judgment, and language [6,7]. The second comprises a wide range of neuropsychiatric symptoms clustered in psychotic (as delusion, hallucinations, and aberrant motor activity) and emotional symptoms (as agitation, dysphoria, anxiety, irritability, and apathy), and which are commonly referred to as behavioral and psychological symptoms of dementia (BPSD) [8,9,10]
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