Introduction:

Neurons above your eyes - help control impulses

Neurons on side of your brain - learned to interpret language and music

Neurons towards the top of your head - became specialists in arithmetic and judgement

Neurons underneath - sorted out visual information couriered from back of your eyeballs

Brain’s “Achilles Heal” - very molecules that make our brain work can destroy us

Molecule - group of atoms bound together

Thiamin (veyr important) - hydrogen, oxygen, carbon & nitrogen atoms

Deoxyribonucleic acid(DNA) - hydrogen, oxygen, carbon, nitrogen, & phosphorus

Cup of water - septillion water molecules

Mutants - altered DNA sequences

Rebels - aberrant proteins

Recalcitrant proteins - cause us to hallucinate, erupt in anger, descend into dementia

Molecular neurology - answer to thee common cognitive ailments that continue to plague our brains

Part 1: DNA Mutants

Dr Friedrich Miescher - near-deaf Swiss doctor who stayed in his lab n the mid 1800s

What did Miescher do? - Collect used bandages and scrape their contents into beakers

What dd Miescher find? - in addition to molecules known, cells in the pus contained a stringy material rich in phosphorus

Results of Miescher’s findings - the threadlike isolates soon became known as DNA (forgotten for 80 years)

Importance from protein switched due to who? - Dr. Oswald Avery in 1944

What and where did he work? - Nearly retired Canadian bacteriologist; worked in Rockefeller Institute in NYC

Why did he leave clinical medicine? - Felt powerless treating patients suffocating from lung disease - he left to understand the bacterium called pneumococcus

How did Avery figure out proteins weren’t the critical molecule of heredity? - He added a chemical to kill proteins int he infectuous bacteria but it had very little effect. The harmless bacteria still learned to become infectious meaning proteins didn’t pass down traits.

How did he find out DNA was the important molecule? - He destroyed thee DNA in the debris from the infectious bacteria and the innocuous bacteria could not become dangerous

Chapter 1: In Suspension

Who was the Huntigton’s Disease patient?

Amelia Ellman - 26 years old - gymnast

What was her chance at getting the disease?

50%

How was her childhood?

bad suffered financially, got evicted, lived in a trailer park, trailer park got robbed and they moved to a dingy apartment, then to a motel

Sequence of sounds her mom mad?

Scratch, Profantiy, bump, profanity, screech, profanity

How did Amelia escape this?

She called social services on her mother - went to alcoholic and narcatics anonymous meetings, and eventually started working at a hello kitty store in the mall

How did Amelia come back and take care of her mother?

She used her saved up money to pay off the motel bills - she wanted to put her in a nursing home in case of an accident but they all said she couldnt force her mother to go

Why was the test Amelia took to determine if she had Huntigton’s Disease important?

the molecular test was developed using one of the most fortuitous discoveries in medical history

Who was Nancy Wexler?

23 year old owman in 1968 who learnes her mother had Huntigton’s

How was Huntington’s able to be identified?

In 1979, scientists figured they could use DNA around the Huntington’s disease gene as a proxy for the gene itself - study the region not the specific gene

What was the proposed solution?

They would take tiny molecular scissors to differentiate the short sequence of DNA around the disease gene - length of DNA fragment would correlate with whether or not the person had a normal Huntington’s disease gene or one that causes affliction

What was the problem for this proposed solution?

The gene would need to be tagged, and the tag needed would have to stick within 30 million nucleotides of the gene and fewer than 20 such tags existed worldwide and the odds of them working were dismal

What did David Housman do?

He had an optimistic view on the use of tags

Who was Jim Gusella?

young Canadian geneticist who would earn the nickname Lucky Jim

Who were the Gene Hunters?

Group of scientists led by Wexler in 1993 identified the exact nucleotide sequence of the huntington’s disease gene

Sequence of the Huntington’s disease?

CAG-CAG up to 35 times & people who develop the disease have it 40 times or more

The sequence is responsible for the production of a dangerous flimsy protein that clogs brain cells

How to stop the condition from developing?

Researchers designed a drug that prevents the protein’s production

How many CAG repeats did Amelia have?

46

Chapter 2: La Bobera De La Familia - “the idiocy of the family”

What’s simple about Huntington’s disease?

It is a one-gene, one-disease affliction

How is this different from Alzheimer’s?

It is the culmination of poorly understood genetic and environmental risk factors

Who was Hector Montoya?

Hailing from Antioquia, Columbia, his family had been wracked by early-onset Alzheimer’s fro two centuries and he was in his forties when he could no longer work - hospitalized by Dr. Francisco Lopera

What was Hector’s problem?

His hippocampus had basically disappeared

Who was Dr. Kenneth Kosik?

American neurologist with expertise in biology of the Alzheimer’s disease - started helping Lopears with Hector’s family case

Who was Dr. Alois Alzheimer and who did he treat?

Discovered memory loss in Auguste Deter who was in an asylum in Frankfurt, Germany in 1888

Renowned for his skills with the microscope

• She was just 51 when she was put in the mental hospital after forgetting recipes, yelling at her husband etc.

What was the results of Dr.Alzheimer’s questioning?

Auguste was able to identify all objects but not able to recollect the interactions minutes after but she remembered long-known facts

Why was 1901 significant?

Year of academic inspiration but also personal tragedy - his wife got really sick and dies; widowed at 37

• He took his three kids and moved to Munich where he became the pupil of psychiatrist Emil Kraepelin

What happened April 9, 1906?

An interns from the asylum in Frankfurt called to inform that Auguste Deter has passed the previous day and sent her brain to Dr.Alzheimer

What was wrong with Auguste’s brain?

it was a fraction of the normal size, cerebral cortex valleys and gaps had become wide and flimsy

Her brain had long, tangly substances accumulating in her neurons, and plaque had appeared which was reminiscent of specimens from older patients with dementia

*University of Tubingen where Alzheimer presented was also where Miescher discovered DNA

How did Kraepelin help Alzheimer?

He garnered attention by devoting several paragraphs of Alzheimer and Auguste in the new edition of his textbook and first used the term “Alzheimer’s Disease”

How did Alzheimer die?

he enjoyed his fame for less than a decade and dies December 19, 1915 after a cold had turned into a corrosive heart infection and died at 51, same age as Auguste when they had first met

*Lopera got the brain of a 56 year old woman who had dies of La Bobera and sent it to Kosik

What is special about La Bobera?

It is molecularly uniform and a purer malady as its not as vulnerable to cofounders since most people get it in their forties

It is also fairly predictable compared to that of a regular Alzheimer patient’s progression

What gene mutate for people with la bobera?

The Presenilin 1 gene - builds a protein that acts like a waste-processing center for trash and recycle

With the mutations - molecules that owuld have been recycles are broken into toxic parts that accumulate in plaques - hallmark of Alzheimer’s

What was the first research trial?

In 2013, a drug that change the insoluble clump of plaques to a soluble form that immune cells could clean up

Chapter 3: Has Anyone Seen My Father?