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3.2.4. Department of Laboratory Department activities
From a neuropathological point of view, Alzheimer's The Department of Laboratory is focused on the
disease (AD) is a neurodegenerative disease that af- study of biomarkers and susceptibility genes for Alz-
fects specific areas of the brain, altering the circuits heimer's disease. This study has the following primary
involved in the catecholaminergic, serotonergic and objectives: to gain further insight into the molecular
cholinergic transmission. AD pathophysiology inclu- basis of the disease and to develop predictive al-
des the presence of neuritic amyloid plaques, neu- gorithms that combine information on genetic, bio-
rofibrillary tangles, neuronal loss and neurochemical chemical and neuroimaging markers with
abnormalities. diagnostic, prognostic or responsive to disease-mo-
difying therapies markers.
Neuritic plaques contain extracellular deposits of β-
amyloid peptide surrounded by dystrophic neurites, For this purpose, the Department's research is con-
activated microglia and reactive astrocytes. These nected with the activities of the Multidisciplinary Sup-
peptides derive from the β-amyloid precursor pro- port Unit, and the Departments of Neuroimaging,
tein (APP) through the sequential processing by dif- Neuropathology and BT-CIEN on the two main rese-
ferent proteolytic complexes called β and arch projects in the CIEN Foundation and Queen
γ-secretases. Sofia Foundation: the Alzheimer project and the Va-
llecas project.
Neurofibrillary tangles (NFT) are intraneuronal bodies
composed of paired and helically wound filaments Because of its location in the CAFRS, the UIPA is best
(paired helical filaments, PHF) of a hyperphosphory- placed for obtaining biological samples from pa-
lated form of the microtubule-associated protein, tients with minimal discomfort for them and their fa-
tau. The NFT appear in many of the dystrophic neu- milies.
rons around amyloid plaques. Currently, many rese-
archers believe that both the development of The Alzheimer Project
amyloid plaques and NFT formation represent relati-
vely late events in the progression of the disease, The Alzheimer Project focuses on regular and proto-
which may or may not reflect the fundamental bio- col-based monitoring of a cohort of CAFRS patients
chemical-molecular dysfunctions that trigger the di- with dementia, ether as residents at the Center or at-
sease. tendants at the Day Center, with the main objective
of investigating the final stages of Alzheimer's dise-
The clinical manifestations of AD are preceded by ase. Patients are recruited into the monitoring pro-
an asymptomatic preclinical phase, after which the gram after signing an Informed Consent by a family
first symptoms appear in the prodromal phase of the member or guardian. The Alzheimer Project program
disease characterized by mild cognitive impairment consists of i) a biannual clinical and neuropsycholo-
(MCI). In this regard, AD can be viewed as an on- gical assessment by the Multidisciplinary Support Unit
going process that evolves from the asymptomatic (UMA. for its acronym in Spanish), ii) a biannual
phase to the dementia stages. This progression is lar- blood sampling, coincident with the usual one taken
gely determined by genetic risk variants and is asso- at the residence, iii) conducting an annual cranial
ciated with biochemical changes that may ideally MRI if the patient's condition allows it, and iv) dona-
serve as early markers of the disease. tion of brain tissue after patient's death.
CIEN Foundation Annual Report 2015 / 58
