Type of presentation: Poster

LS-11-P-5824 VASCULAR COMPLICATIONS LINKED TO ALZHEIMER’S DISEASE

Bester J.¹, Buys A. V.², Lipinski B.³, Kell D. B.⁴, Pretorius E.¹

¹Department of Physiology, Faculty of Health Sciences, University of Pretoria, South Africa, ²MicrMicroanalysis Unit, University of Pretoria, South Africa, ³Joslin Diabetes Center, Harvard Medical School, Boston, USA, ⁴School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK

janette.bester@up.ac.za

Introduction: Current literature suggests that vascular components play a fundamental role in

neurological diseases like Alzheimer’s disease (AD) (Kovacic and Fuster, 2012). One such

component is erythrocytes (RBCs) that are highly deformable, which contributes to assisting

blood flow in the microcirculation (Mohandas and Gallagher, 2008). Abnormalities in RBCs and

their flow can contribute to AD by obstructing oxygen delivery to parts of the brain that are

already in a compromised state. Closely linked to hematological pathology in AD are increased

iron levels that may play an important role in the pathogenesis of the condition(Barnham and

Bush, 2008). Increased iron levels cause oxidative stress, as they participate in

oxygen-dependent free radical formation (Castellani et al., 2012). This free radical stress may

have an impact on RBCs and may possibly cause extensive and accumulative damage to these

cells, ultimately compromising their functioning. Aims: Determine if there is iron overload

present in AD and if this has an effect on the structure of the RBCs. Methods: 25 AD patients

and 40 healthy control individuals were studied and results from light microscopy, scanning

electron microscopy, atomic force microscopy and confocal microscopy were correlated.

Results: RBC ultrastructure showed a changed morphology in the presence of iron overload.

These changes might impair the oxygen carrying capacity and compromise hemorheology of

the RBCs, and additionally cause a strain on the already challenged brain function of these

individuals. Conclusions: Iron overload are present in AD patients, this may cause the condition

to progress faster than in AD individuals who do not have iron overload, particularly due to the

additional hydroxyl radical load.

References:

Kovacic,J.C.,andFuster,V.(2012). Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease. Mt. SinaiJ.Med. 79, 664–673.

Mohandas,N.,andGallagher,P.G.(2008) .Red cell membrane:past,present,and future. Blood 112, 3939–3948.

Barnham,K.J.,andBush,A.I.(2008). Metals in Alzheimer’s and Parkinson’s diseases. Curr.Opin.Chem.Biol. 12, 222–228.

Castellani,R.J.,Moreira,P.I.,Perry,G.,andZhu,X.(2012). The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors 38, 133–138.

We would like to acknowledge Dr Prashilla Soma who drew our blood

samples and Dr Wiebren Duim (Neurologist) who gave us insights regarding the Alzheimer’s

patient sample. Also, we are in debt to the family members of the patients who gave informed

consent for the study.

Fig. 1: Red blood cell (RBC) of a healthy individual with a typical discoid shape. Scale: 1μm	Fig. 2: Discoid shaped red blood cell from an Alsheimer's patient with normal serum ferritin levels. Scale: 1μm
Fig. 3: Irregular shaped red blood cells from Alzheimer's patient with increased serum ferritin levels. Scale: 1μm