Raman Imaging Reveals Accumulation of Hemoproteins in Plaques from Alzheimer’s Diseased Tissues

Abstract

Hemes have been suggested to play a central role in Alzheimer's disease since they show high peroxidase reactivity when bound to Amyloid beta peptides, leading to the production of reactive oxygen species. Here we used Fourier transform infrared and Raman imaging on Alzheimer's diseased mice and human brain tissue. Our finding suggests the accumulation of hemes in the senile plaques of both murine and human samples. We compared the Raman signature of the plaques to the ones of various hemeoproteins and to the hemin-Aβ-42 complex. The detected Raman signature of the plaques does not allow identifying the type of heme accumulating in the plaques.

The Role of Heme and Copper in Alzheimer’s Disease and Type 2 Diabetes Mellitus

“…These depositions considerably weaken the cerebral vessel walls causing a high chance of rupture and hemorrhage. , Thus, the microhemorrhages and consequent heme exposure inside the brain might authenticate the possibility of the heme involvement in disease etiology. The colocalization of heme-rich deposits together with Aβ plaques are confirmed in AD by staining the affected brain. , The heme hypothesis has its confirmative evidence from the recent researches that established heme-Aβ binding in vitro , which might account for heme deficiency and other cytopathology observed in AD. ,,− Thus, all these findings collectively propose heme to be another key to the Alzheimer’s pathogenesis. It is notable that heme-bound Aβ can behave as peroxidase and can catalyze the oxidation of many significant biomolecules in H 2 O 2 medium which can be portrayed as a reason for abnormal neurotransmission and cognitive decline. , T2Dm also shows much similar inclusion of heme in its etiology.…”

“…The colocalization of heme-rich deposits together with Aβ plaques are confirmed in AD by staining the affected brain. 24 , 109 The heme hypothesis has its confirmative evidence from the recent researches that established heme-Aβ binding in vitro , which might account for heme deficiency and other cytopathology observed in AD. 67 , 102 , 110 − 112 Thus, all these findings collectively propose heme to be another key to the Alzheimer’s pathogenesis.…”

Biological Oxidations and Nitrations Promoted by the Hemin–Aβ16 Complex

“…Interestingly, an abnormal heme b concentration has been observed in the temporal brain of AD patients with up to a 2.5-fold increase with respect to controls [23]. Moreover, a recent Raman study suggests the accumulation of heme in the senile plaques of human samples, although the type of the heme (i.e., free heme or from a hemoprotein) is still unclear [24]. The dysfunction of regulatory heme pathways, hemin complexation, by Aβ peptides and its subsequent pro-oxidase effect have been proposed to play a role in AD progression.…”

Spin state dependent peroxidase activity of heme bound amyloid β peptides relevant to Alzheimer's disease

“…4,27,31,39 Recent Raman imaging of AD brain tissue has revealed that, heme present in Ab plaques in the brain tissue resembles a six coordinated lowspin species that may possibly be a bis-His low-spin heme-Ab species. 40 Heme has been shown to bind to the Ab peptide through the histidine side chain and depending on the cofactor to peptide ratio or concentration, heme-Ab complexes can have different coordination environments and spin states. 22,41,42 When heme and Ab are present in 1 : 1 stoichiometry and at low concentrations, the resultant complex is a high-spin one with an axial His ligation and a weakly bound trans-axial water derived ligand (Fig.…”

“…4,27,31,39 Recent Raman imaging of AD brain tissue has revealed that, heme present in Aβ plaques in the brain tissue resembles a six coordinated low-spin species that may possibly be a bis-His low-spin heme–Aβ species. 40…”