Iron levels hasten Alzheimer’s disease



High levels of iron in the brain could increase the risk of developing Alzheimer’s disease and hasten the cognitive decline that comes with it, new research suggests.

The results of the study, which tracked the brain degeneration of people with Alzheimer’s over a seven-year period, suggest it might be possible to halt the disease with drugs that reduce iron levels in the brain.

 “We think that iron is contributing to the disease progression of Alzheimer’s disease,” neuroscientist Scott Ayton, from the University of Melbourne in Australia, told Anna Salleh at ABC Science.

“This is strong evidence to base a clinical trial on lowering iron content in the brain to see if that would impart a cognitive benefit.”

Alzheimer’s is a devastating disease that researchers suspect “begins when two abnormal protein fragments, known as plaques and tangles, accumulate in the brain and start killing our brain cells,” explains Fiona Macdonald for ScienceAlert.

It starts by destroying the hippocampus – the region of the brain where memories are formed and stored – and eventually damages the region where language is processed, making it difficult for advanced Alzheimer’s patients to communication. As the disease’s gradual takeover continues, people lose the ability to regulate their emotions and behaviour, and to make sense of the world around them.

But previous studies have shown that people with Alzheimer’s disease also have elevated levels of brain iron, which may also be a risk factor for the disease.

“There has been debate for a long period of time whether this is important or whether it’s just a coincidence,” Ayton told ABC Science.

The long-term impact of elevated iron levels on the disease outcome has not been investigated, the researchers say.

So Ayton’s team decided to test this, examining the link between brain iron levels and cognitive decline in three groups of people over seven years. The participants included 91 people with normal cognition, 144 people with mild cognitive impairment, and 67 people with diagnosed Alzheimer’s disease.

At the beginning of the study, the researchers determined the patients’ brain iron levels by measuring the amount of ferritin in the cerebrospinal fluid around the brain. Ferritin is a protein that stores and releases iron.

The researchers did regular tests and MRI scans to track cognitive decline and changes in the brain over the study period.

They found that people with higher levels of ferritin – in all groups – had faster declines in cognitive abilities and accelerated shrinking of the hippocampus. Levels of ferritin were also a linked to a greater likelihood of people with mild cognitive impairment developing Alzheimer’s.

Their data contained some other interesting takeaways: The researchers found higher levels of ferritin corresponded to earlier ages for diagnoses – roughly three months for every 1 nanogram per millilitre increase.

They also found that people with the APOE-e4 gene variant, which is known to be the strongest genetic risk factor for the disease, had the highest levels of iron in their brains.

This suggests that APOE-e4 may be increasing Alzheimer’s disease risk by increasing iron levels in the brain, Ayton told ABC Science.

The researchers say their findings, which were published in the journal Nature Communications, justify the revival of clinical trials to explore drugs to target brain iron levels.

In a study carried out 24 years ago, a drug called deferiprone halved the rate of Alzheimer’s cognitive decline, Ayton told Clare Wilson at NewScientist. “Perhaps it’s time to refocus the field on looking at iron as a target.”

“Lowering CSF ferritin, as might be expected from a drug like deferiprone, could conceivably delay mild cognitive impairment conversion to Alzheimer’s disease by as much as three years,” the team wrote.

Three fundamental issues about Alzheimer’s

Three fundamental issues about Alzheimer’s:

 three fundamental issues about Alzheimer's

three fundamental issues about Alzheimer’s


” It has been known for years that Alzheimer ‘s disease in a region of the brain called the entorhinal cortex, ” said co -author Scott A. Small , MD , Boris Katz and Rose Professor of Neurology , professor of radiology and director of the Alzheimer’s Disease Research Center . ” But this study is the first to show in living patients starting specifically in the lateral entorhinal cortex , or LEC . LEC is considered a gateway to the hippocampus, which plays a key role in the consolidation of long memory term , among other functions. If the LEC is affected, also affected other aspects of the hippocampus. ”

With time , spreads Alzheimer LEC directly to other areas of the cerebral cortex , in particular the parietal cortex , a brain region involved in various functions including spatial orientation and navigation. Researchers suspect that Alzheimer “functionally ” , ie , to compromise the function of neurons in the LEC , which in turn threatens the integrity of neurons in adjacent areas spreads .

A third important finding of the study is that a LEC impairment when changes in tau and amyloid precursor protein (APP ) co -exist occurs . ” The LEC is especially vulnerable to Alzheimer ‘s disease because it typically accumulates tau , which sensitizes the LEC to the accumulation of APP . Together, these two proteins damage neurons in the LEC , setting the stage for Alzheimer ‘s disease ” said lead co -author Karen E. Duff , PhD , professor of pathology and cell biology ( in psychiatry and in the Taub Institute for Research on Alzheimer ‘s Disease and the Aging Brain ) at CUMC and the Psychiatric Institute of the State of New York.

Researchers used a high-resolution variant of functional magnetic resonance imaging to map metabolic defects in the brains of 96 adults who participated in the Project Aging Washington Heights – Inwood Columbia ( WHICAP ) . All adults were free of dementia at the time of registration.

” Study Dr. Richard Mayeux WHICAP allows us to follow a large group of healthy elderly individuals , some of whom have gone on to develop Alzheimer ‘s disease ,” said Dr. Small. “This study has given us a unique opportunity to image and characterize patients with Alzheimer’s disease in its early , preclinical phase. ”

The 96 adults were followed for an average of 3.5 years , at which time 12 individuals who have progressed to mild Alzheimer’s disease were found. An analysis of functional magnetic resonance basis of these 12 individuals found a significant decrease in cerebral blood volume ( CBV ) – A measure of the metabolic activity of the LEC – compared to the 84 adults who were free of dementia.

A second part of the study the role of tau and APP was addressed in the LEC dysfunction. While previous studies have suggested that dysfunction of the entorhinal cortex is associated with abnormalities in both tau and APP , it was not known how these proteins interact to drive this dysfunction , particularly in preclinical Alzheimer .

To answer this question , explained first author Usman Khan, a MD- PhD student from the laboratory of Dr. Small , the team created three mouse models , one with elevated levels of tau in the LEC , one with high levels APP , and one with high levels of both proteins. The researchers found that the LEC dysfunction occurred only in mice with both tau and APP .

The study has implications for both research and treatment. ” Now that we have established clearly where Alzheimer’s begins , and showed us that these changes are observable by fMRI, we may be able to detect Alzheimer’s disease at an early preclinical stage , when the disease may be treatable and before spreading to other regions of the brain , “said Dr. Small. In addition , the researchers say , the new imaging method could be used to evaluate the effectiveness of promising drugs during early Alzheimer ‘s disease .

The paper is entitled ” Molecular conductors and lateral entorhinal cortex dysfunction in preclinical Alzheimer ‘s disease cortical spreading . ” Other contributors are Li Liu, Frank Provenzano, Diego Berman, Caterina Profaci , Richard Sloan and Richard Mayeux , all CUMC .

Marijuana and Alzheimer’s Disease Pathology

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology:

A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology

Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer’s disease.

Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC), in the 1960’s, this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.

The active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis.

In these contexts, efficacy results from THC binding to the family of cannabinoid receptors found primarily on central and peripheral neurons (CB1) or immune cells (CB2). More recently, a link between the endocannabinoid system and Alzheimer’s disease has been discoveredwhich has provided a new therapeutic target for the treatment of patients suffering from Alzheimer’s disease. New targets for this debilitating disease are critical as Alzheimer’s disease afflicts over 20 million people worldwide, with the number of diagnosed cases continuing to rise at an exponential rate. These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.Yet, it is important to note that in these reports, cannabinoids serve as signaling molecules which regulate downstream events implicated in Alzheimer’s disease pathology and are not directly implicated as effecting Aβ at a molecular level.

Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβ aggregation, and this provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.